micro_mod7

• traveler's (nonbloody diarrhea)
• enterotoxins LT & ST
• non-invasive
• Ferments sorbitol (EHEC does not)

• heat labile toxin (LT) stimulates adenylate cyclase (like cholera). Addition of adenosine diphosphate-ribose (ADP ribosylation) to the G protein that stimulates the cyclase. Irreversibly activates cyclase. Increase in AMP, stimulating cAMP-dependent protein kinase, which phosphorylates ion transportes in the membrane; export ions, causes an outpouring of fluid,
• potassium, and chloride from enterocytes to lumen of gut

-heat stable toxin (ST) activates guanylate cyclase (not able to reabsorb Na)

• do not cause inflammation, do not invade intestinal mucosa, and cause watery, nonbloody diarrhea – stool looks like rice water (just like cholera)

intestinal tract infection

gram neg rods

• most abundant facultative anaerobe in the colon and feces

traveler’s diarrhea, watery non-bloody, tissue invasion is absent, localized colonization

• • traveler’s diarrhea (Moctezuma’s revenge): watery diarrhea, acquired by ingestion of food or water contaminated with human feces, non-bloody,
• self-limited, short duration (1-3 days); “turista”. Infection w/ enterotoxigenic E. Coli

• ferments lactose – distinguishes from Shigella and Salmonella

• O157:H7; INVASIVE
• SHIGA TOX (vero, phage, AB, 28S rRNA)
• HUS (when shiga tox enters bloodstream, worse when treat with antibiotics)
• Doesn't ferment sorbitol
• Type II
• Pedistal Formation
• daycare centers

-EXOTOXIN VEROTOXIN (SHIGA TOXIN); CAUSES CPE

SYSTEMIC INFECTION CAUSES BLOODY DIARRHEA (DYSENTERY) BC TOXIN AND INFLAMMATORY CYTOKINES DAMAGE BLOOD VESSELS IN THE LAMINA PROPIA; INFLAMMATORY CELLS (NEUTROPHILS) IN THE STOOL

INHIBITS PROTEIN SYNTHESIS BY REMOVING ADENINE FROM THE 28S rRNA RIBOSOME

• hemolytic-uremic syndrome (HUS) is life-threatening complication of EHEC; verotoxin enters bloodstream. Have thrombocytopenia, hemolytic anemia, and acute renal failure (last 2 due to presence of verotoxin receptors on surface of endothelium of small blood vessels and on surface of kidney epithelium). Hemolytic anemia occurs when RBC pass through damaged area and become distorted (schistocytes) and then lyse. Thrombocytopenia bc platelets adhere to damaged endothelial surface. Renal failure due to death of kidney epithelial cells. Shiga-like toxins reach the bloodstream

*ENCODED BY TEMPERATE (LYSOGENIC) BACTERIOPHAGES

• • TYPE II SECRETION SYSTEM (SHIGA-LIKE TOXIN) SEC DEPENDENT, REQUIRES 2 STEPS: 1) PROTEINS SECRETED W/SIGNAL PEPTIDES THAT TARGET THEM TO SEC OR RELATED MACHINERY FOR TRANSPORT ACROSS THE CYTOPLASMIC
• MEMBRANE INTO THE PERIPLASM 2) IN PERIPLASM, PROTEIN DESTINED FOR SECRETION FOLDS INTO ITS NATIVE CONFORMATION AS IT IS PASSED ON TO AN ADDITIONAL SECRETION COMPLEX WITH A PILLUS-LIKE STRUCTURE WHICH THEN GUIDES THE FOLDED
• PROTEIN TO THE EXTERIOR THROUGH A SECRETION CHANNEL IN THE OUTER MEMBRANE

• bloody diarrhea – dysentery, abdominal cramping,
• fever like Shigella

• main reservoir is cattle, acquired from
• undercooked meat such as hamburger in fast food restaurants (requires few bacteria – 50 CFU per gram of hamburger); also due to direct contact with
• animals; (causes hemorrhagic colitis- non-febrile,
• bloody diarrhea)

-tissue invasion is absent, colonize large intestine but remain localized to the mucosal surface of the gut

• - Modify the host actin and cytoskeletal elements in
• order to form a characteristic attaching and effacing lesion of the brush border: “pedestal formation”

(ENTEROPATHOGENIC E. COLI)

-NON-BLOODY DIARRHEA IN INFANTS/KID, SELF-LIMITED, ESPECIALLY IN DEVELOPING COUNTRIES, LESS COMMON IN THE US.

NO TOXINS IDENTIFIED.

• -MODIFY THE HOST ACTIN AND CYTOSKELETAL ELEMENTS IN
• ORDER TO FORM A CHARACTERISTIC ATTACHING AND EFFACING LESION OF THE BRUSH BORDER à “PEDESTAL FORMATION” (LIKE EHEC)

• NEONATAL DIARRHEA: CAUSED BY O55 AND O111

TYPE III SECRETION SYSTEM; SEC DEPENDENT

WITHIN AND OUTSIDE ENTERIC TRACT

• GI infection: pili for jejunum and ileum; not large int.
• UTI (catheters)
• Neonatal meningitis & sepsis
• Sepsis (capsule & endotox)

• UTI: MOST COMMON CAUSE OF THIS TYPE OF INFECTION. ACCOUNTS FOR 80% OF ALL UNCOMPLICATED UTI.

• ACCOUNTS FOR ONLY 20% OF
• COMPLICATED INFECTIONS. CAUSES UTI
• DUE TO PATIENT’S OWN COLONIC FLORA THAT COLONIZES THE UROGENITAL AREA. O SEROTYPES CAUSE THIS; UROPATHIC STRAINS HAVE PILI WITH ADHESIN PROTEINS THAT BIND TO
• SPECIFIC RECEPTORS. BINDING SITE ON THESE RECEPTORS CONSISTS OF DIMMERS OF GALACTOSE (GAL-GAL DIMERS). PRIMARILY IN WOMEN BC IT’S EASIER TO ASCEND INTO BLADDER/KIDNEY: 1) SHORTER URETHRA 2) PROXIMITY OF URETHRA TO ANUS 3) COLONIZATION OF VAGINA BY MEMBERS OF FECAL FLORA.

• MOST FREQUENT CAUSE OF
• NOSOCOMIAL UT INFECTION DUE TO INDWELLING CATHETERS.

• NEONATAL MENINGITIS: ALSO A MAJOR CAUSE TOGETHER WITH GROUP B STREP. SOURCE IS MOTHER’S BIRTH CANAL AS A RESULT OF COLONIZATION IN 25% OF PREGNANT WOMEN, ACQUIRED DURING BIRTH. CAPSULAR TYPE K1 ANTIGEN

• CYSTITIS, S/S DYSURIA (PAINFUL URINATION), FREQ URINATION,
• URGENCY (NEED TO URINATE W/O DELAY).

• TYPE 1 PILI, SPECIFIC FOR MANNOSE CONTAINING STRUCTURES; BC OF AN
• AFFINITY FOR THE BLADDER.

• NON-INVASIVE
• KIDNEY INFECTION: PYELONEPHRITIS, S/S FEVER, CHILLS, FLANK PAIN,
• FLANK TENDERNESS, PRESENCE OF PERIPHERAL LEUKOCYTOSIS. URINE CONTAINS WBC CASTS
• DUE TO INVOLVEMENT OF RENAL TUBULES. BACTEREMIA MAY OCCUR W/ ASSOCIATED SHOCK AND DEATH.

• TYPE P PILI BIND A SPECIFIC DIGAL RECEPTOR OF THE P BLOOD GROUP
• ANTIGEN, SO THEY ARE CALLED PAP PILI (PYELONEPHRITIS-ASSOCIATED PILI)
• COMPLICATONS: RENAL ABSCESSES. INVASIVE

• • SEPSIS: ORGANISM MOST FREQUENTLY ISOLATED FROM PT’S W/
• HOSPITAL-ACQ SEPSIS, ARISES FROM URINARY, BILIARY, OR PERITONEAL INFECTIONS.
• PERITONITIS IS USUALLY A MIXED INFECTION (E. COLI OR OTHER
• FACULTATIVE ENTERIT GRAM NEG ROD + ANAEROBIC MEMBERS OF THE COLONIC FLORA LIKE BACTEROIDES
• AND FUSOBACTERIUM

• GRAM NEG RODS

• • MOST ABUNDANT FACULTATIVE ANAEROBE
• IN COLON AND FECES, BUT OUTNUMBERED BY OBLIGATE ANEROBES SUCH AS BACTEROIDES

MOTILE

INDOLE+

PILI, CAPSULE, ENDOTOXIN (LPS --> DIC), 3 EXOTOXINS (ENTEROTOXINS -- 2 CAUSE WATERY LT & ST AND 1 BLOODY VERO)

• FERMENTS LACTOSE – DISTINGUISHES FROM SHIGELLA AND SALMONELLA

• • MACCONKEY’S AGAR : LACTOSE FERMENTERS ARE PINK,
• BOTH SELECTIVE AND DIFFERENTIAL; IT SELECTS FOR GRAM NEG
• (BILE SALTS INHIBIT GRAM +) AND DIFFERENTIATES BTW LACTOSE FERMENTERS AND
• NON-LACTOSE FERMENTERS

EMB (EOSIN-METHYLENE BLUE) AGAR: GREEN SHEEN

• -TSI (triple sugar irone) shows acid slant
• and acid butt with gas but no H2S

- LD test for lysine decarboxylase, +, purple (SALMONELLA TOO)

- ONPG test for B-galactosidase, + yellow (ONLY E. COLI)

- isolation of enterotoxigenic or enteropathogenic E.Coli from pt’s w/ diarrhea is NOT a routine dx procedure

• PRODUCES INDOLE FROM TRYPTOPHAN

• DECARBOXYLATES LYSINE

• USES ACETATE AS ITS ONLY SOURCE OF CARBON

• O157:H7 (EHEC) DOES NOT FERMENT SORBITOL ON MACCONKEY’S AGAR, COLORLESS COLONIES (DISTINGUISHES FROM OTHER STRAINS)

• • 3 ANTIGENS: 1) THE O, OR CELL WALL, ANTIGEN; 2) H, OR FLAGELLAR, ANTIGEN; 3) THE K, OR CAPSULAR,
• ANTIGEN

• • MORE THAN 150 O, 50 H, AND
• 90 K ANTIGENS, RESULTING IN MORE THAN 1000 ANTIGENIC TYPES

• • indwelling urinary
• catheters predispose to UTI intravenous lines predispose to sepsis

• • being a women predispose to UTIs
• • urinary reflux
• • physiological or neurological malfunctions that may prevent proper
• urinary voiding
• • urinary tract stones
• • neonatal meningitis, colonization of this organism in pregnant women
• (occurs in 25%)

UTI: ORAL PEN OR TRIMETHOPRIM-SULFAMETHOXAZOLE

SEPSIS: THIRD-GEN CEPHALOSPORINS (CEFOTAXIME) W/ OR W/O AMINOGLYCOSIDE (GENTAMICIN)

NEONATAL MENINGITIS: COMBO OF AMPICILLIN AND CEFOTAXIME

• REHYDRATION FOR TRAVELER’S,
• ANTIBIOTIC RESISTANCE DUE TO B-LACTAMASE

• - ABX TX FOR DIARRHEAL DISEASES NOT INDICATED, BUT ADMIN OF TRIMETHOPRIM-SULFA
• + LOPERAMIDE (IMODIUM) SHORTENS DURATION OF SYMPTOMS

EHEC O157:H7 STRAINS WITH ABX (CIPROFLOXACIN) INCREASES THE RISK OF DEVELOPING HEMOLYTIC-UREMIC SYNDROME BY INCREASING THE AMOUNT OF VEROTOXIN RELEASED BY THE DYING BACTERIA

• •PREVENTION: FOR UTI JUDICIOUS
• USE AND PROMPT WITHDRAWAL OF CATHETERS

• RECURRENT INFECTIONS, PROPHYLAXIS W/ URINARY ANTISEPTIC DRUGS
• (NITROFURANTOIN OR TRIMETHOPRIM-SULFA), CRANBERRY JUICE BC TANNINS INHIBIT THE BINDING OF THE PILO TO THE BLADDER EPITHELIUM

FOR SEPSIS- SWITCH IV LINES

• TRAVELER’S- EAT COOKED FOOD ABROAD, PROPHYLAXIS BY DOXYCYCLINE, CIPROFLOXACIN,
• TRIMETHOPRIM-SULFA, OR PEPTO-BISMOL, AVOID UNCOOKED FOODS AND DRINKING
• UNPURIFIED WATER

EHEC- DO NOT EAT UNDERCOOKED MEAT

-NO VACCINE

• • TYPHOID FEVER: BEGINS IN SMALL INTESTINE BUT FEW GI SYMPTOMS.
• ONSET OF ILLNESS IS SLOW W/ FEVER, CONSTIPATION.

WITHIN AND OUTSIDE ENTERIC TRACT

PRIMARY BACTEREMIA IN MONOCYTES OF PEYER’S PATCHES, SPREAD TO PHAGOCYTES OF LIVER, GALLBLADDER, SPLEEN, AND MESENTERIC LYMPH NODES (PT IS ASYMPTOMATIC STILL)

SECONDARY BACTEREMIA-TISSUE INVASION: 10-14 DAYS LATER, HIGH FEVER CAUSED BY ENDOTOXIN, HEADACHE (BLOOD CULTURES NOW POS), DELIRIUM, TENDER ABDOMEN, ENLARGED SPLEEN, ROSE SPOTS (MACULES ON ABDOMEN), MAY HAVE LEUKOPENIA, ANEMIA, ABNORMAL LIVER FN TESTS. RESOLVES THE 3RD WK.

• 4-8 WK PHASE, ORGANISM SURVIVES AND GROWS W/IN PHAGOSOMES, POSSIBLE
• INVASION OF THE GALLBLADDER AND KIDNEY. FEVER, SHAKING CHILLS (DUE TO
• SEPTICEMIA), HEADACHE, MUSCLE PAIN,
• CHRONIC CARRIER STATE IN 3%,
• ORGANISMS FORM BIOFILMS ON THE GALLSTONES OF PATIENTS, AND EXCRETION OF BACTERIA IN THE FECES:
• INTESTINAL HEMORRHAGE OR PERFORATION.

• AUTOIMMUNE DISEASES SUCH AS REITER’S SYNDROME (TRIAD OF ARTHRITIS, CONJUNCTIVITIS, AND URETHRITIS). IMMUNE COMPLEXES MAY PLAY A ROLE

• GRAM NEG RODS

INVASIVE FACULTATIVE INTRACELLULAR

• DO NOT FERMENT LACTOSE, COLORLESS COLONIES ON MACCONKEY’S OR EMB AGAR

• PRODUCE H2S

• 1 SEROTYPE (BASED ON EWING)

• • REQUIRES A HIGHER DOSE, AROUND 100,000 ORGANISMS (MUCH MORE
• THAN SHIGELLA): HIGH INFECTIOUS DOSE B/C INACTIVATED IN STOMACH

• MOTILE

• PLASMID ABX MEDIATED RESISTANCE

• • PHASE VARIATION:
• -SALMONELLA CAN CONTROL WHICH OF THE H ANTIGENIC TYPES OF FLAGELLA IT
• PRODUCES

• O ANTIGENS (OUTER POLYSACCHARIDES OF CELL WALL) SUBDIVIDES INTO GROUPS A-I.

• • FLAGELLAR H ANTIGENS: PHASE 1 AND 2
• (ONLY 1 IS SYNTHESIZED)

CONTACT-DEPENDENT

SEC INDEPENDENT

REQUIRES LOW CA++ ENV.,

• SECRETION MACHINERY HAS 20 PROTEINS, WHICH FORM A CHANNEL SPANNING THE
• CYTOPLASMIC BACTERIAL MEMBRANE, THE PERIPLASM, AND THE OUTER BACTERIAL MEMBRANE.

OUTER TIP FUSES W/ HOST CELL MEMBRANE TO FORM AN “INJECTION PORE”, ALLOWING INJECTION OF TOXIC PROTEINS DIRECTLY FROM THE BACTERIAL CYTOPLASM INTO THE HOST CELL CYTOPLASM

• Vi CAPSULE
• PATHOGENICITY ISLAND
• TYPE III SECRETION

• INFECTS CELLS OF THE RETICULOENDOTHELIAL SYSTEM (LIVER AND SPLEEN)

• PLASMID-ENCODED FIMBRIAE ALLOW ATTACHMENT TO THE MICROVILLI OF ENTEROCYTES

• ENDOTOXIN (LPS) CAUSES FEVER AND SHOCK ASSOC W/ SEPSIS;

BINDS TO CD14 ON MACROPHAGES --> IL-1, IL-6, AND TNF. IL-1 --> FEVER.

ACTIVATES COMPLEMENT CASCADE --> C3A (HYPOTENSION) + C5A (NEUTROPHIL RECRUITMENT) AND ACTIVATES COAG CASCADE VIA HAGEMAN FACTOR (FACTOR XII) --> DISSEMINATED INTRAVASCULAR COAGULATION (DIC)

•Vi (CAPSULE) ANTIGEN ANTIPHAGO

• NO EXOTOXINS

• • ENTERS CELL BY PATHOGEN-DIRECTED ENDOCYTOSIS (RUFFLED MEMBRANES AT
• ENTRY SITE) BY TYPE III SECRETION
• SYSTEM (GENE ENCODED ON SALMONELLA PATHOGENICITY ISLAND)- PROMOTES
• SALMONELLA ENTRY AND PREVENTS PHOSOME-LYSOSOME FUSION

-PATHOGEN IS RELEASE OUT BASAL SIDE TO LAMINA PROPRIA

-LIVE IN INACTIVE MACROPHAGE

• DX: GRAM+ RODS, BLOOD CULTURE DURING THE 1ST 2 WKS OF ILLNESS, BONE MARROW CULTURES ARE USUALLY +, STOOL CULTURES MAY BE + (ESPECIALLY IN
• CHRONIC CARRIERS);

• COLORLESS COLONIES ON
• MACCONKEY’S OR EMB AGAR

• TSI SHOWS ALKALINE SLANT &
• ACID BUTT, NO GAS AND ONLY
• SMALL AMOUNTS OF H2S (NO BLACK COLOR IN BUTT)

- LD TEST FOR LYSINE DECARBOXYLASE, +, PURPLE (E.COLI ALSO)

- ONPG TEST FOR B-GALACTOSIDASE, -, COLORLESS (E.COLI+)

• - WIDAL TEST: RISE IN AB TITER
• IN PT’S SERUM

• PREDISPOSED:
• • ↓ stomach acid due to
• antacids predisposes to Salmonella

• • carrier rate higher for
• women with gallbladder disease and gallstones

• TX: CEFTRIAXONE OR CIPROFLOXACIN

• CHORNIC CARRIERS -- AMPICILLIN OR CIPROFLOXACIN: RESISTANCE DUE TO
• B-LACTAMASE

- CHOLECYSTECTOMY MAY BE NECESSARY TO ABOLISH CHORNIC CARRIER STATE

-FOCAL ABSCESSES DRAINED SURGICALLY

• PREVENTION: PUBLIC HEALTH MEASURES AND PERSONAL HYGIENE MEASURES (HAND WASHING), CHLORINATION OF WATER, SEWAGE DISPOSAL,

• -2 VACCINES FOR HIGH RISK
• (OCCUPATIONAL RISK) AND TRAVELERS: 1 W/ Vi POLYSACCHARIDE CAPSULE (IM)
• AND 1 W/ LIVE, ATTENUATED S. TYPHI AS IMMUNOGEN (ORALLY). PROVIDE
• LIMITED PROTECTION (50-80%), BOTH EQUALLY EFFECTIVE.

• - NEW CONJUGATE VACCINE W/
• CAPSULAR POLYSACCHARIDE Vi ANTIGEN + CARRIER PROTEIN IS IMMUNOGENIC IN YOUNG CHILDREN, BUT NOT AVAILABLE IN US

ENTEROCOLITIS: INVASION OF EPITHELIAL AND SUBEPITHELIAL OF SMALL AND LARGE INTESTINES. PENETRATE BOTH THROUGH AND BTW MUCOSAL CELLS INTO LAMINA PROPRIA, RESULTING IN INFLAM AND DIARRHEA.

WITHIN AND OUTSIDE ENTERIC TRACT

BACTEREMIA IS INFREQUENT.

INCUBATION 12-48 HRS;

VOMITING, ABD PAIN, DIARRHEA FROM MILD TO SEVERE, W/ OR W/O BLOOD.

SELF-LIMITED, NO MEDICAL CARE EXCEPT IN VERY YOUNG AND VERY OLD.

• • SEPSIS W/ METASTATIC ABSCESSES.
• 5-10% OF SALMONELLA INF OCCURS WHEN PT 1) HAS A CHRONIC DISEASE LIKE
• SICKLE CELL ANEMIA OR CANCER 2) CHILD WITH ENTEROCOLITIS -- PREVIOUSLY DAMAGED TISSUES (INFARCTS AND
• ANEURYSMS) MOST FREQUENT SITES OF METASTATIC ABSCESSES

• • BACTEREMIA – TISSUE INVASION:
• RESULTS IN SEEDING OF MANY ORGANS W/ OSTEOMYELITIS, PNEUMONIA, AND MENINGITIS AS THE MOST COMMON SEQUELAE. THINK “OSTEOMYELITIS
• IN A CHILD W/ SICKLE CELL ANEMIA”

• • IMPORTANT CAUSE OF VASCULAR GRAFT
• INFECTIONS

• • HIGH INCIDENCE OF CERTAIN AUTOIMMUNE DISEASES SUCH
• AS REITER’S SYNDROME, CHARACTERIZED BY THE TRIAD OF ARTHRITIS, CONJUNCTIVITIS, AND URETHRITIS. IMMUNE COMPLEXES MAY PLAY A ROLE

facultative gram neg rods

• do not ferment lactose, colorless colonies on MacConkey’s or EMB agar

• produce H2S

• motile

• >1500 serotypes

• • requires a higher dose, around 100,000 organisms
• (much more than Shigella): high infectious dose b/c it is inactivated in stomach

• O antigens (outer polysaccharides of cell wall) subdivides into groups A-I

• flagellar H antigens: phase 1 and 2 (only 1 is synthesized)

• plasmid ABX mediated resistance

enteric tract of humans/animals; human sources are either persons who temporarily excrete the organism during or shortly after an attack of enterocolitis or chronic carriers who excret the organism for years;

animal sources is usually pultry and eggs, or inadequate cooked meat products. Dogs, turtles, snakes, lizards, iguanas are additional sources.

• • transmission by fecal-oral route, ingestion
• of food and water contaminated by human and animal wastes• one of the most common causes of bacterial enterocolitis in US

• Host defense:
• • PMN leukocyte response limits infection of enterocolitis to the gut and the adjacent mesenteric lymph nodes

• • differentiated epithelial cells prevent invading organisms from penetrating, pH variances (1 in stomach, 9 in ampulla of Vater), mucin (mucous coating) in small intestine, peristaltic motion of bowel,
• presence of lysozymes, proteases, lipases, bile salts, etc., secretory IgA, phagocytes, and lymphoid cells, indigenous host intestinal flora which compete for available nutrients and secrets bacteriocins (inhibitory substances)

• Predisposing factors:
• • having a chronic disease like sickle cell predisposes to sepsis bc pt’s are asplenic, so they have difficulty clearing encapsulated bacteria

• child w/ enterocolitis

• HIV infected pt’s w/ low CD4 count, have more severe diarrhea and more serious metastatic infections

Vi CAPSULE

• endotoxin causes fever and shock assoc w/ sepsis;

binds to CD14 on macrophages, stimulates release of Il-1, Il-6, and TNF. IL-1 --> fever.

• activate complement cascade -- C3a
• (hypotension) + C5a (neutrophil recruitment) and activate coagulation cascade via Hageman factor (Factor XII), potentiall resulting in disseminated intravascular coagulation (DIC)

• no exotoxin

• type III secretion system:

Dx: gram stain and culture, isolation from stool sample;

• colorless colonies on MacConkey’s or EMB
• agar

• TSI shows alkaline slant & acid butt, gas and H2S
• (black color in butt) are produced

- LD test for lysine decarboxylase, +, purple (ALSO E.COLI)

- slide agglutination test: serogroup A, B, C, D, or E based on O antigen

• • Tx: self-limited disease, resolves w/o tx; antibiotics
• usually not recommended bc they may prolong excretion of the organisms, increase the frequency of the carrier state, and select mutants resistant to
• the ABX; ceftriaone for sepsis

- use of antimicrobial agents for neonates or persons w/ chronic diseases at risk of septicemia and disseminated abscesses.

• Prevention: public health measures, pasteurization of milk, proper cooking of poultry, eggs, and meat

no vaccine

* MOST EFFECTIVE PATHOGENS AMONG THE ENTERIC BACTERIA

PRIMARILY ENTERIC

• ENTEROCOLITIS (BACILLARY DYSENTERY), BLOODY DIARRHEA, INVADES CELLS OF MUCOSA OF DISTAL ILEUM AND COLON;

LOCAL INFLAM ACCOMPANIED BY ULCERATION, RARELY PENETRATE THROUGH THE WALL OR ENTER THE BLOODSTREAM, UNLIKE SALMONELLAE. INCUBATION PERIOD OF 1-4 DAYS,

FEVER, ABDOMINAL CRAMPS, FOLLOWED BY DIARRHEA, RESOLVING IN 2-3 DAYS

• SOME TISSUE INVASION LOCALIZED IN LARGE INTESTINE

• NO CHRONIC CARRIER

• NO INVASION OF BLOODSTREAM

• AUTOIMMUNE DISEASES SUCH AS REITER’S SYNDROME, CHARACTERIZED BY THE TRIAD OF ARTHRITIS, CONJUNCTIVITIS, AND URETHRITIS. IMMUNE COMPLEXES MAY PLAY A ROLE

• FACULTATIVE GRAM NEG RODS

• NON-LACTOSE FERMENTING, COLORLESS COLONIES ON MACCONKEY’S OR EMB AGAR

• NONMOTILE BC NO H ANTIGEN

• NO H2S PRODUCTION

• NO GAS FROM FERMENTATION OF GLUCOSE

• • LOW INFECTIOUS DOSE B/C
• RESISTANT TO STOMACH ACID

• EXPRESSION OF PARTICULAR O ANTIGENS OF LPS CHARACTERIZES THE SPECIES: A, B, C, AND D, S. DYSENTERIA, S. FLEXNERI, S. BOYDII, AND S. SONNEI RESPECTIVELY

• PLASMID ABX MEDIATED RESISTANCE

• DYSENTERY-TYPE STOOL, BLOODY DIARRHEA (INTESTINAL CELL DIES AND BECOMES PART OF BLOODY DIARRHEA)

• ONLY REQUIRES A VERY SMALL AMOUNT (10 ORGANISMS), ID50

• •HABITAT: HUMAN COLON ONLY, NO
• ANIMAL RESERVOIR

• • TRANSMISSION BY FECAL-ORAL ROUTE
• - THE 4 F’S: FINGERS, FLIES, FOOD, AND
• FECES (FACTORS OF TRANSMISSION),

• USUALLY IN DAY-CARE NURSERIES AND
• MENTAL HOSPITALS

• S. DYSENTERIA CAUSES MOST SERIOUS ILLNESS, WHILE S. SONNEI IS PREDOMINANT IN U.S.

• NOT NORMAL INTESTINAL FLORA

• PREDISPOSING FACTORS
• • CHILDREN YOUNGER THAN 10
• YRS OF AGE, ELDERLY PT’S

• SHIGA TOXIN (PHAGE, AB, 28S rRNA)
• ACTIN-BASED MOTILITY

• • INVADES MUCOSA OF ILEUM AND COLON BUT DOESN’T PENETRATE FARTHER
• (SEPSIS IS LOWER THAN SALMONELLA)

• SPECIALIZED MECHANISM FOR PENETRATING MUCOSAL SURFACE: INITIALLY ENTER M CELLS DUE TO OUTER MEMBRANE PROTEINS CALLED INVASION PLASMID ANTIGENS (IPA)

• INTERNALIZED BACTERIA ESCAPE VACUOLES AND USE ACTIN-BASED MOTILITY, ONCE IN LAMINA PROPRIA, SHIGELLA CAN INVADE BASAL SURFACE OF EPITHELIAL CELLS; INDUCES CYTOKINES AND PMNS WHICH SEPARATE TIGHT JUNCTION AND ALLOW SHIGELLA TO FURTHER INVADE CAUSING DYSENTERY-TYPE STOOL, BLOODY DIARRHEA DUE TO CELL DEATH AND EXUDATION OF INFLAMMATORY CELLS

• • SHIGA TOXIN (ENTEROTOXIN) CRITICAL FACTOR FOR PATHOGENESIS, ENCODED BY LYSOGENIC BACTERIOPHAGES. INHIBITS PROTEIN SYNTHESIS BY INACTIVATION OF
• 60S RIBOSOME; 2-COMPONENET (A:B) EXOTOXIN THAT ACTS INTRACELLULARLY ON VILLUS CELLS. A ACTS ON 28S rRNA, INACTIVATING 60S RIBOSOMAL SUBUNIT BLOCKING CHAIN ELONGATION AND PROTEIN SYNTHESIS --> CELL DIES, BECOMES PART OF BLOODY DIARRHEA

• SERUM AGGLUTININS NOT HELPFUL BC THERE’S NO BACTEREMIA

• TYPE III SECRETION SYSTEM

• DX: GRAM STAIN AND CULTURE,

COLORLESS COLONIES ON MACCONKEY’S OR EMB AGAR

• Methylene blue stain: see if neutrophils are
• present. If they are, invasive organism present SUCH AS SHIGELLA, SAL, OR CAMPY (NOT E.COLI, V.CHOLERA, OR C.PERFRINGENS

PRODUCE ALKALINE SLANT AND ACID BUTT IN TSI AGAR BUT NO GAS AND NO H2S

- U TEST FOR UREASE, -, YELLOW

• - LD TEST FOR LYSINE DECARBOXYLASE, -,
• AMBER

-SLIDE AGGLUTINATION: DETERMINES GROUP

• • TX: FLUID AND ELECTROLYTE REPLACEMENT IN MOST CASES, NO ABX (FOR SEVERE CASES: FLUOROQUINOLONE SUCH AS CIPROFLOXACIN,
• TRIMETHROPRIM-SULFA AS ALTERNATIVE.

ANTIPERISTALTIC DRUGS ARE CONTRAINDICATED BC THEY PROLONG FEVER, DIARRHEA, AND EXCRETION OF ORGANISM

• • PREVENTION:
• PUBLIC HEALTH MEASURES, PROPER SEWAGE DISPOSAL, CHLORINATION OF WATER, PERSONAL HYGIENE, PROPHYLACTIC ABX NOT RECOMMENDED,

NO VACCINE

• ZOONOTIC INFECTIONS

• ACUTE GASTROENTERITIS

• NOT REALLY ENTERIC, BUT CAUSES DIARRHEA

• CAN CAUSE BLOOD TRANSFUSION-RELATED SEPSIS AND SHOCK

• MESENTERIC LYMPH NODES MAY BECOME ENLARGED

• MIMIC ACUTE APPENDICITIS

• • HIGH INCIDENCE OF CERTAIN
• AUTOIMMUNE DISEASES SUCH AS REITER’S SYNDROME, CHARACTERIZED BY THE TRIAD OF ARTHRITIS, CONJUNCTIVITIS, AND URETHRITIS. IMMUNE COMPLEXES MAY PLAY A ROLE

• GRAM NEG RODS

• NON-LACTOSE FERMENTER, COLORLESS COLONIES

• CAN GROW IN REFRIGERATED FOODS

• • CAN MULTIPLY IN BLOOD OR BLOOD PRODUCTS STORED REFRIGERATED FOR
• SEVERAL WKS

• • PLASMID MEDIATED OUTER MEMBRANE AG ASSOCIATED W/ ANTIPHAGOCYTIC AND
• PREVENTION OF OPSONIZATION

• PD TEST FOR PHENYLALANINE DEAMINASE IS -, LIGHT YELLOW COLONIES

• VP (VOGES-PROSKAUER) TEST FOR ACETOIN PRODUCTION, -, LIGHT YELLOW COLONIES

• LD TEST FOR LYSINCE DECARBOXYLASE, -, AMBER COLONIES

• U TEST FOR UREASE, +, RED-PURPLE

• SOURCE : WILD AND DOMESTIC ANIMALS

• • HUMANS BECOME INFECTED BY
• INGESTION OF MILK, FOOD, OR WATER CONTAMINATED W/ ANIMAL FECES (MORE NOTABLE IN COLDER CLIMATES)

• • CROSSES INTESTINAL MUCOSA
• THROUGH M CELLS IN TERMINAL ILEUM AREA

VIABLE IN COLD ENV

• • RELATIVELY INVASIVE
• EXTRACELLULAR PATHOGEN

• • MULTIPLE ANTI-PHAGOCYTIC
• CAPABILITIES

• • PRODUCES TOXIN SIMILAR TO
• STABLE TOXIN OF ETEC

• TYPE III SECRETION SYSTEM -- EXOTOXIN EXO S IS THE ONE MOST CLEARLY ASSOCIATED W/ VIRULENCE --> ADP RIBOSYLATION OF RAS PROTEIN (DAMAGES
• CYTOSKELETON)

same diseases as ETEC but more severe

colonizes small intestine and produces enterotoxin choleragen (like LT of e.coli inc cAMP, but on chrom and not plasmid).

• watery diarrhea, rice-water stool (nonbloody effluent), no abdominal
• pain, other symptoms due to dehydration

PRIMARILY ENTERIC

-NO tissue invasion, localized colonization

-loss of fluids and electrolytes --> cardiac and renal failure

-bicarbonate and potassium in stool --> acidosis and hypokalemia

- mortality rate w/o tx --> 40%

• curved, Comma-shaped gram neg rods

• ferment sucrose (yellow colonies on TCBS)

• oxidase pos ***

• highly motile

produces mucinase to attach

• 2 groups based on O cell wall antigen: O1 group (epidemic disease) and non-O1 (sporadic disease). O1 serotype --> 2 biotypes: E1 Tor and classical and 3 serotypes --> Ogawa, Inaba, Hikojima

• genes for cholera toxin are encoded by a temperate ss DNA bacteriophage CTX (lysogenic conversion)

• • requires a higher dose, around 100,000 organisms
• (much more than Shigella):

• human colon, animal reservoir

• human carriers are frequently asymptomatic --> individuals in incubation period or convalescing
• animal carriers --> marine shell-fish, shrimp, oysters, ingestion of these w/o adequate cooking cause disease

• transmission by fecal oral route

• Predisposing factors
• • poor sanitation, malnutrition, overcrowding, inadequate medical services

• pt’s taking antacids

• pt’s w/ gastrectomy

• Choleragen (ENTEROTOX, AB5, PHAGE, GM1 GANGLIOSIDE - RECEPTOR FOR TOXIN)
• mucinase
• TcP A
• VERY SUSEPTIBLE TO STOMACH ACID
• O1 - EL TOR & CLASSICAL

• adherence to cells of brush border of the gut, then secrete bacterial enzyme mucinase --> dissolves glycoprotein coating over the intestinal cells, enhances attachment to intestinal mucosa

• • massive watery diarrhea caused by enterotoxin
• (choleragen, A-B subunits) that activates adenylate cyclase by adding ADP-ribose to Gs (A subunit)

• ↑ cAMP causes loss of H20 and ions --> massive watery diarrhea --> morbidity and death due to dehydration and electrolyte imbalance

• A sub (ADP-ribosylating activity) and 5 Bs
• (binds) to GM1 ganglioside- cell surface receptor of cholera toxin

• TcpA: toxin co-regulated pili allow adherence (pili synthesis is regulated the same as toxin)

• type II secretion system

• • Dx: gram stain and culture, stool sample show colorless colonies on MacConkey’s agar bc lactose
• is fermented slowly

OXIDASE+

• -on TSI agar: acid slant and
• acid butt, NO gas or H2s bc it ferments sucrose

• - Thiosulfate-citrate-bile-salts-sucrose
• (TCBS) agar: ferments sucrose (yellow
• colonies)

-agglutination of organism by polyvalent O1 or non-O1 antiserum

-retrospective dx: rise in Ab titer

• • Tx: fluid and electrolyte replacement (oral
• rehydration therapy or IV)

• tetracycline not necessary but shortens duration
• of symptoms and excretion of organism

• • Prevention- public health measures, clean water and
• food supply, rehydration and electrolyte therapy

-vaccine containing killed cells has limited effectiveness --> 50%, doesn’t interrupt transmission. Recommended for travelers.

Tetracycline for prevention is effective in close contacts, can’t prevent spread of major epidemic. Prompt detection of carriers to limit outbreaks.

• diarrhea, from mild to severe, nausea, vomiting, abdominal cramps, fever, illness is self-limited, lasting about 3 days

• Comma-shaped gram neg rods

• marine organisms, grows in warm sea water

• grows in 8% NaCl solution: halophilic ***: requires high NaCl to grow

• doesnt ferment sucrose

• • transmitted by ingestion of raw or
• undercooked seafood (shellfish such as oysters)…sushi!

• major cause of diarrhea in Japan where raw fish is eaten in large quantities, infrequent in US

• enterotoxin similar to choleragen is secreted and limited invasion sometimes occurs

• • Dx: Thiosulfate-citrate-bile-salts-sucrose
• (TCBS) agar: does not ferment sucrose (green colonies)

• Tx: illness is self-limiting (lasts 3 days)

• • Prevention: proper refrigeration and
• cooking of seafood

• cellulitis, especially shelfish handlers, who often sustain skin wounds

• life-threatening sepsis with hemorrhagic bullae

• Comma-shaped gram neg rods

• marine organisms, grows in warm sea water

• are halophilic: requires high NaCl to grow, will grow in 1% NaCl BUT NOT 8%

• acquired by trauma to skin (shellfish handlers) or ingestion of raw shellfish in immunocompromised or have liver disease

• Predisposing factors
• •immunocompromised pt’s

• pt’s w/ chronic liver disease (cirrhosis)

• Dx:
• TCBS agar: does not
• ferment sucrose (green colonies)

• Tx: doxycycline

• Preventon:
• wear gloves

PRIMARILY ENTERIC

• • Curved, gram neg rods, appear either comma
• or S-shaped

• microaerophilic, grows best in 5% oxygen rather than 20% atmosphere

• grows well at 42°C

• oxidase positive

• sensitive to nalidixic acid

• no lactose fermentation

• urease neg

• zoonotic disease

• motile: characteristic of this bacteria, helps colonize gut

• • enterocolitis, especially in children. Seems to be enterotoxin-mediated syndrome (similar to cholera
• toxin)

-major cause of diarrhea in the US

-begins w/ watery, foul-smelling diarrhea followed by bloody stools, fever, severe abdominal pain

-bloody stool occurs w/ invasion. Systemic infections (BACTEREMIA) in neonates and debilitated adults

• • common antecedent of Guillain-Barre syndrome (autoimmune disease, targets myelin protein), common cause of acute neuromuscular paralysis, due to formation of Abs vs. C. jejuni that cross-react w/
• antigens on neurons

• associated w/ reactive arthritis as well

• • autoimmune diseases such
• as Reiter’s syndrome, characterized by the triad of arthritis, conjunctivitis, and urethritis. Immune complexes may play a role

• • Dx: gram stain, culture, biopsy specimens of gastric
• mucosa, urease-pos, “urea breath” test-ingest
• radiolabeled urea, radiolabeled CO2 is evolved, radioactivity detected on breath

-Test for Helicobacter antigen in stool

-Presence of IgG Abs in patient’s serum

• • Tx: duodenal ulcers:
• Amoxicillin, metronidazole, and bismuth salts (pepto) --> inhibits growth

• Prevention: none, no vaccine

• • Dx: gram stain plus culture from stool sample, on
• blood agar plate containing ABX which inhibit other fecal flora --> Skirrow’s agar (vancomycin + trimethroprim+ cephalothin + polymyxin + amphotericin B…, at 42°C in 10% Co2, low O2
• (microaerophilic env.)

• -CAMPY blood agar:
• selective medium, organism is susceptible to nalidixic acid and resistant to cephalothin

• • Tx: symptomatic, erythromycin or ciprofloxacin in
• enterocolitis

• Prevention: Public health measures, proper sewage disposal, personal hygiene

no vaccine

• Curved gram neg rod (similar to campylobacters)

• urease pos

• • has not been isolated in stool, food, water, or
• animals; however probably person-to-person b/c clustering in families

PRIMARILY IN ENTERIC TRACT

• Gastritis

• duodenal peptic ulcer* recurrent pain in the upper abdomen, w/ bleeding of GI tract

• NO bacteremia or disseminated disease

• risk factor for gastric carcinoma

• • linked to MALT lymphomas
• • habitat: human stomach

• transmission by ingestion

• rate of infection in developing countries is high

• attaches to the mucus-secreting cells of the gastric mucosa

• synthesize urease, which produces ammonia that damages gastric mucosa --> predisposes to gastritis and peptic ulcer

• ammonia neutralizes stomach acid allowing organism to live

• pain in upper abdomen, no bacteremia

• • Dx: gram stain, culture, biopsy specimens of gastric
• mucosa, urease-pos, “urea breath” test-ingest
• radiolabeled urea, radiolabeled CO2 is evolved, radioactivity detected on breath

-Test for Helicobacter antigen in stool

-Presence of IgG Abs in patient’s serum

• • Tx: duodenal ulcers:
• Amoxicillin, metronidazole, and bismuth salts (pepto) --> inhibits growth

• Prevention: none, no vaccine

OUTSIDE ENTERIC ONLY (KES grp)

• lactose fermenting, pink colonies in MacConkey’s or EMB

• • facultative gram neg rods w/ large
• polysaccharide capsule (impedes phagocytosis) --> mucoid appearance

• produces big mucoid colonies bc of its large polysaccharide capsule --> K polysaccharide antigen

• primary, nonopportunistic

• carried in Resp tract of 10% of healthy ppl

• • Pneumonia (predisposed to by chronic pulmonary disease) -produces a thick, bloody sputum (“currant-jelly”sputum), can progress to necrosis and abscess
• formation

• • UTI : nosocomial infection due to indwelling urinary
• catheter

• human upper resp and enteric tracts

• transmitted by aspiration and inhalation of respiratory droplets

•UTI by ascending spread of fecal flora

• sepsis due to endotoxins in cell wall

• BACTEREMIA may occur, especially to meninges

• endotoxin causes fever and shock assoc w/ sepsis; binds to CD14 on macrophages (LIKE E.COLI AND SAL, ENT.BACTER), stimulates release of Il-1, Il-6, and TNF. IL-1 --> fever. Can activate complement cascade --> C3a (hypotension) + C5a (neutrophil recruitment) and activate coagulation cascade via Hageman factor (Factor XII), potentiall resulting in disseminated intravascular coagulation (DIC)

• no known exotoxin

• • Dx: gram stain and culture, characteristic mucoid
• colonies, pink colonies in MacConkey’s or EMB

- VP (Voges-Proskauer) tests for acetoin production, + pink-red

- K antigen identified by Quelling Rxn (capsular swelling)

• Tx: Cephalosporins w/ aminoglycosides

NO VACCINE

OUTSIDE ENTERIC TRACT ONLY (KES grp)

GRAM- RODS, NORMAL FLORA OF GUT

ox-, cat+

• hospital acquired pneumonia, UTI, sepsis due to endotoxins in cell wall

• Complicated UTI may be the result of nosocomial infection due to indwelling urinary catheter

• hospitals: invasive procedures such as IV catheterization, resp intubation, UT manipulations

• • endotoxin causes fever and shock assoc w/ sepsis;
• binds to CD14 on macrophages (E.COLI, SAL, KLEBSIELLA), stimulates release of Il-1, Il-6, and TNF. IL-1 --> fever. Can activate complement cascade --> C3a (hypotension) + C5a (neutrophil recruitment) and activate coagulation cascade via Hageman factor (Factor XII), potentiall resulting in disseminated intravascular coagulation (DIC)

• Tx
• • Highly antibiotic resistant

• use aminoglycoside (gentamicin) and cephalosporin (cefotaxime) used before tests are known

• Prevention
• • changing site of IV catheters, removing urinary catheters when not needed, proper care of resp therapy devices

NO vaccine

OUTSIDE ENTERIC TRACT ONLY (KES grp)

• enteric gram-neg rod

• red-pigmented colonies in blood agar (at 25 C but NOT at 37 C)

• LATE lactose fermenter, can produce neg rxn

• hospital acquired pneumonia

• UTI and sepsis due to endotoxins in cell wall

• Complicated UTI may be the result of nosocomial infection due to indwelling urinary catheter

• due to contaminated water in resp therapy devices

• endotoxin causes fever and shock assoc w/ sepsis;

binds to CD14 on macrophages (E.COLI, SAL, KES grp), stimulates release of Il-1, Il-6, and TNF. IL-1 --> fever. Can activate complement cascade --> C3a (hypotension) + C5a (neutrophil recruitment) and activate coagulation cascade via Hageman factor (Factor XII), potentiall resulting in disseminated intravascular coagulation (DIC)

• Tx
• • Highly antibiotic resistant

• use aminoglycoside (gentamicin) and cephalosporin (cefotaxime) used before tests are known

• Prevention
• • changing site of IV catheters, removing urinary catheters when not needed, proper care of resp therapy devices

NO vaccine

OUTSIDE ENTERICS ONLY (PPM grp)

• • facultative gram neg rods
• • non lactose-fermenting, colorless colonies on MacConkey’s or EMB agar
• urine smells like dirty socks...

HIGHLY MOTILE HELPS INVADE UT: SWARMING MOTILITY

• habitat: human colon and environment

• transmission: to urinary tract by ascending spread of fecal flora, especially in women

• • UTI -community and hospital acquired
• - complicated UTI frequently associated w/ urinary tract stone formation due in part to the enzyme
• urease which splits urea to form ammonium hydroxide. This raises the pH of the urine and facilitates the formation of struvite calculi, or stones.

• endotoxn causes fever and shock assoc w/ sepsis

• urease degrades urea to produce ammonia, ­pH

•leads to “struvite” stones”

• sepsis

• produce urease , urea to form NH3 and CO2, raises pH producing alkaline urine, encourages formation of stones (calculi) called “struvite” composed of magenesium ammonium phosphate, obstructing urinary flow, damages epithelium, serves as a nidus for recurrent infection trapping bacteria in stone

• produce enzyme phenylalanine deaminase

• antigens of OX strains of P. vulgaris cross-react w. many rickettsiae

•Dx: gram stain and culture- “swarming” effect over blood agar due to motility (expanding rings/waves of organisms over the surface of the agar)

-blood agar w/ phenylethyl alcohol inhibits swarming, allowing isolated colonies

- PD test for phenylalanine deaminase is +, green

• Tx: Trimeth-sulfa or ampicillin, but 3rd gen cephalosporin for serious infections

- resistant to ABX

-keeping urine at low pH

• • Prevention- no vaccine, removal of
• catheter to prevent UTI

OUTSIDE ENTERIC TRACT ONLY (PPM grp)

• UTIs and sepsis -community and hospital acquired

• enteric gram neg

• • highly motile, helps invade
• urinary tract

• • produces urease, urea to form NH3 and CO2, raises pH producing alkaline urine, encourages formation of stones (calculi) called “struvite” composed of magenesium ammonium phosphate,
• obstructing urinary flow, damages epithelium, serves as a nidus for recurrent infection trapping bacteria in stone

• produce enzyme phenylalanine deaminase

• indole pos

• habitat: human colon and environment

• transmission: to urinary tract by ascending spread of fecal flora, especially in women

• TX:
• • indole pos

• keeping urine at low pH

• frequently resistant to multiple ABS

Prevention: removal of catheter

• wound infection

• UTI and sepsis

• Complicated UTI may be the result of nosocomial infection due to indwelling urinary catheter

• can spread to the skin, where they cause a black, necrotic lesions: ecthyma gangrenosum

• pneumonia

• • nosocomial infections in burn pts and people w/ chronic respiratory disease, like Cystic Fibrosis: most
• common cause of chronic pulmonary infection in CF pt’s.

• pt’s w/ lowered host defense (PMN lower than 500/uL): predisposing factor

• pt’s w/ indwelling catheters à predisposing factor

• mortality rate: 50%

• endocarditis in IV drug users (like staph aureaus)

• severe external otitis (malignant otitis externa) and other skin lesions (folliculitis) occurs in users of swimming pools and hot tubs in which the chlorination is inadequate

• most common cause of osteochondritis of the foot in those who sustain puncture wounds through the soles of gym shoes

• corneal infections are seen in contact lens users

• strict aerobic gram-neg rods

• nrg from oxidation of sugars, NOT fermentation: non-fermenters, colorless colonies

• pyocyanin (blue-green) pigment produced, fruity odor produced: damages cilia and mucosal cells of the resp. tract

• Pyocins are encoded on plasmids, they are bacteriocins (ABX-like substances that have a lethal effect on other bacteria).

• oxidase-pos (oxidation involves e- transport by cytochrome c)

• able to withstand disinfectants

• scavenging iron and phosphate: essential for survival!!!

The majority of iron in serum is bound by transferrin. Pseudomonas produces siderophores that compete for the bound iron. If iron is scarce, the production of elastase and exotosin A cause tissue damage that results in more accessible iron. When phosphate levels are limited, the organism increases production of phospholipase C which hydrolyzes phospholipids making phosphates availbe from host eukaryotic membranes.

• environmental water sources (hospital, tap water), soil

• skin, upper respiratory tract and colon in 10% of people

• • ability to grow in simple aqueous solutions has
• resulted in contamination of resp therapy and anesthesia equipment, IV fluids, and distilled water

• • endotoxin causes fever and shock assoc w/ sepsis;
• binds to CD14 on macrophages, stimulates release of Il-1, Il-6, and TNF. IL-1 --> fever. Can activate complement cascade --> C3a (hypotension) + C5a (neutrophil recruitment) and activate coagulation
• cascade via Hageman factor (Factor XII), potentiall resulting in disseminated intravascular coagulation (DIC)

• • produces exotoxin A which acts like diptheria toxin, ADP-ribosylation of EF2, inhibiting protein
• synthesis --> causes tissue necrosis

• pili mediate attachment, capsule prevents phagocytosis

•glycocalyx strains in CF pts: slime in which alginate is a prominent component à may play a role in attachment to epithelial cells, promotion of biofilm formation, and interference w/ immune recognition.

• • also, in CF pt’s, the core polysaccharide of LPS adheres to chloride channel protein and allows
• attachment to lung cells

• type III secretion system

• • enzymes such as elastase and protease: are
• histotoxic and facilitate invasion of the organism into the bloodstream

• • pyocyanin damages the cilia and mucosal cells of the
• respiratory tract

• • Dx: gram stain and culture, prduce 2 pigments:
• 1) pyocyanin, which can color the pus in a wound blue, and
• 2) pyoverdin (fluorescein), a yellow-green pigment that fluoresces under UV light (detection of skin infection in burn patients) -these pigments diffuse into the agar, imparting a blue-green color

- TSI agar: typical metallic sheen of the growth on this agar, coupled w/ the blue-green pigment on ordinary nutrient agar and a fruity aroma

-dx confirmed by biochemical rxns

-id done by bacteriophage or pyocin typing

• Typing of pyocins isolates is used in epi tracking of outbreaks caused by this organism – endogenous vs. exogenous; environmental sources; nosocomial; associations btw pt’s; associations w/ hospital personnel, etc. Typing is based on the observation that Pyocin will only inhibit the growth of a limited # of other bacterial strains. Therefore, clinical isolates, producing different pyocins, will demonstrate characteristic patterns of growth inhibition of known typing strains.

• Tx: antibiotics on the basis of sensitivities b/c resistance is common, resistance to relatively high levels of most ABX in use

• use antipseudomonal penicillin (ticarcillin or piperacillin) + aminoglycoside (gentamicin or amikacin) --> synergistic effect

• • Prevention: disinfection of water related equipment
• in hospital, keep PMN counts above 500/uL, remove indwelling catheters promptly, take special care of burned skin

no vaccine

BACTEROSIDES AND PREVOTELLA grps

• sepsis

• intra-abdominal infections à peritonitis or localized abscess

• local abscesses at the site of a mucosal break, emtastatic abscesses by hematogenous spread to distant organs, or lung abscesses by aspiration of oral flora. Causes disease below the diaphragm.

• infections are endogenous bc they are part of the normal flora, usually arising from a mucosal break, NOT communicable

• • anaerobic, gram neg rods
• • no spores
• • capsule is anti-phagocytic
• • many anaerobic infections contain a mixed facultative and anaerobic flora

• Predisposing factors
• • surgery, trauma, chronic disease
• • local tissue necrosis, impaired blood supply, and growth of facultative anaerobes at the site contribute to anaerobic infections

• • predominant anaerob in human colon
• • found in the vagina of approx. 60% women
• • transmission from colon to blood or peritoneum

LPS IN CELL WALL IS SCHEM DIFF FORM AND LESS POTENT THAN TYPICAL ENDOTOX

POLYSAC CAP

NO EXOTOX

• • Dx: gram stain and culture
• -isolated anaerobically on blood agar plates containing kanamycin and vancomycin to inhibit unwanted organisms

-biochemical rxns (sugar fermentation tests)

-production of certain organic acids (formic, acetic, pripionic acid) which are detected by gas chromatography

• • Tx: metronidazole, clindmycin, chloramphenicol and
• cefoxitin all effective, abscesses should be surgically drained

resistance to penicillin G (B-lactamase), cephalosporins, and aminoglycosides: THE MOST ABX-RESISTANT OF THE ANAEROBIC BACTERIA

• • Prevention: perioperative cefoxitin in
• bowel surgery no vaccine

• • Anthrax: common in animals but rare in humans. Occurs in 3 main forms:
• --cutaneous - panophthalmitis; extreme local edema, malignant pustule, bacterimia, death
• --pulmonary (inhalation)
• --GI

• - cutaneous: lesion is a painless ulcer with a black eschar (crust, scab). Local edema is striking. Lesion = malignant pustule. Can progress to bacteremia and
• death if left untreated

• - pulmonary: “whoolsorter’s disease” begins with nonspecific resp tract symptoms resembling influenza (dry cough, substernal pressure). Rapidly progresses to hemorrhagic mediastinitis, bloody pleural effusions, septic shock, and death. Lungs are infected, but classic features and x-ray picture of pneumonia are not present. Mediastinal widening seen on chest x-ray is an important dx criterion. Hemorrhagic mediastinitis
• and hemorrhagic meningitis are severe life/threatening complications.

- GI: symptoms include vomiting, abdominal pain, bloody diarrhea

• • Aerobic
• • gram-pos rods with square ends, frequently found in chains
• • longer and more deeply staining
• • form spores
• • capsule w/ poly-D-glutamate (antiphagocytic virulence factor) – unique, since capsules of other bacteria are polysaccharides
• • non-hemolytic colonies
• • Anthrax toxin is encoded on one plasmid and the polyglutamate capsule is encoded on a different plasmid
• -capsule is encoded on plasmid pXO2
• -Ab against capsule are not protective

• nonmotile

• spores persist in soil, also found in water

• • humans are most often infected cutaneously at the time of trauma to the skin, which allows the spores on animal products, such as hides, bristles, and wool, to enter
• • pulmonary (inhalation) anthrax occurs when spores are inhaled into the lungs (not communicable from person-to-person) moving rapidly to the mediastinal lymph nodes, where it causes hemorrhagic mediastinitis (leaves the lung so rapidly, reason why it’s not transmitted by the respiratory route to others)

• • GI anthrax occurs when contaminated meat is ingested
• • zoonoses: transmitted btw vertebrate animals and humans
• • no person-to-person transmission

• • 2 exotoxins, known as the anthrax toxin: edema and lethal factor
• • anthrax toxin has 3 components:
• -B (or binding) subunit in each of the 2 exotoxins is protective antigen (PA). Binds to the host cell and is cleaved by a protease. Following its cleavage, the fragment of PA that remains bound can, in turn, bind either EF or LF.

These 2 active components are shuttled into the cytoplasm of the host cell. Both encoded on plasmid pXO12. Ab vs. this protein protects vs. disease (vaccine contains protective antigen as the immunogen)

*The A, or active, subunit has enzymatic activity

-edema factor (an adenylate cyclase): A-B subunit --> inc cAMP causing an outpouring of fluid from the cell into the extracelullar space --> edema (similar to cholera toxin)

• -lethal factor (kills cells by inhibiting cell division) A-B subunit: Protease cleaves phophokinase --> activates the mitogen-activated protein kinase (MAPK) signal
• transduction pathway: growth of human cells, and cleavage of the phosphokinase inhibits cell growth.

-both EF and LF are A-like and encoded on plasmid pXO1

• • Dx: gram stain plus aerobic culture (anthracis is
• non-motile)
• • spores are not seen in smears of exudates bc spores form when nutrients are insufficient and nutrients are plentiful in infected tissue
• • Rapid testing: PCR, direct fluorescent Ab test that detects antigens of the organism in the lesion
• • Serologic tests: ELISA, test for Ab (require acute and convalescent serum samples, can only be used to make a dx retrospectively)

• Tx: Penicillin G, Ciprofloxacin (drug of choice), Doxycycline (alternative drug).

* No resistant strains

• Prevention: Ciprofloxacin or doxycycline used as prophylaxis.

• Vaccine for high-risk people; contains purified protective antigen as immunogen. Six doses of vaccine over an 18-month period.
• Annual boosters for protection.

Incinerating animals that die of anthrax, rather than burying them, will prevent he soil from becoming contaminated with spores.

• Food poisoning

• Two syndromes:
• • Diarrheal form: 8-16 hours later after consumption of contaminated food. Long incubation period (18 hrs) and features watery, nonbloody diarrhea (caused
• by enterotoxin with adenylate cyclase activity; accumulation of fluid in gut) resembling clostridial gastroenteritis, abdominal pain
• -duration ranges from 20-36 hrs
• -caused by germination of spores in the lumen of the gut, followed by the production of heat labile enterotoxin

• • Emetic form: -rapid onset 1-5 hours later, heat-stable toxin. Short incubation period (4 hrs)
• consists primarily of nausea and vomiting, similar to staphylococcal food poisoning, due to injestion of heat-stable toxin.

- example: preparation of fried rice: cooked rice w/o refrigeration and then flash-fried in hot oil insufficient to inactivate the heat-stable toxin

• •Aerobic
• •gram pos rods
• • longer and more deeply staining
• •forms spores

• TRNSMSN:
• • grains and rice
• • spores survive boiling and rapid frying and germinate when rice is kept warm for many hrs (e.g. reheated fried rice)
• • portal of entry: GI tract
• • zoonoses: transmitted btw vertebrate animals and humans
• • no person-to-persontransmission

• •Two enterotoxins:
• - one like cholera toxin: ADP ribose inc cAMP
• w/in enterocyte.
• - other resembles staph enterotoxin:superantigen
• stimulate release of of IL-1 and IL-2 from macrophages and helper T cells, respectively. Prominent vomiting is due to cytokines released from the lymphoid cells --> enteric nervous
• system to activate the vomiting center in the brain. This toxin is fairly heat-ressistant and is therefore
• usually not inactivated by brief cooking. Resistant to stomach acid and enzymes in stomach and jejunum. There are 6 immunologic types (A-F).

•Dx: not done

•Tx: Symptomatic tx given only

• Prevention: no specific means of prevention; rice should not be kept warm for long periods of time

• No vaccine

• • Tetanus (lockjaw)
• risus sardonicus; Opisthotonos, a pronounced arching of the back due to spasm of the strong extensor muscles of the back

Respiratory failure ensues. High mortality rate

• • Tetanus neonatorum / neonatal tetanus (umbilical tetanus): organism enters through a contaminated umbilicus or circumcision wound (major problem in some developing countries due to unsanitary conditions)
• -fatal for neonates of unimmunized mothers
• -mortality rate: 85%
• -localized infection with systemic spread of toxin

• • puncture wounds are more serious than open
• wounds with regard to clostridial infections

• • Anaerobic
• • gram-pos rods
• • longer and more deeply staining
• • form spores “tennis racket”
• • ferment a multitude of organic compounds and degrade biomaterials: important environmental partners in the biodegradation process, but these
• enzymes enhance organisms’ invasiveness and pathogenicity if infection occurs

• • widespread in soil
• • enters through traumatic breaks/wound in skin (e.g. where a nail penetrates the foot, but the spores can also be introduced during “skin-popping,” a technique used by drug addicts to inject drugs into the skin)
• • germination favored by necrotic tissue and poor blood supply in the wound
• • genetic info for toxin is encoded on plasmid

• NO CELL SURFACE COMPONENTS have been identified which act as virulence factors

• • Tetanus toxin (tetanospasmin): exotoxin produced by vegetative cells at the wound site. Polypeptide
• toxin carried intra-axonally (retrograde) to the CNS --> binds to GM1 ganglioside receptors irreersibly and blocks release of inhibitory mediators
• (e.g. glycine and GABA) at spinal synapses BY proteases that cleave the proteins FOR mediator release. Usually remains active localized with systemic
• spread
• -two-component exotoxin (A-B SUBUNITS): enzymatically Active A and target cell Binding B:
• Among the most toxic substances known
• • excitatory neurons are unopposed: muscle spasm
• • lockjaw (trismus) and risus sardonicus (grimace) result
• • only one antigenic type of tetanus toxin

• Dx: clinical, no microbiologic or serologic dx, organisms rarely isolated from wound site.

• Tx: Tetanus immune globulin used to neutralize toxin + penicillin G (or metronidazole…although role of ABX is uncertain) + spasmolytic drugs - benzodiazepines (Valium) + adequate airway and respiratory support should be given

• • Prevention: Toxoid vaccine, only one antigenic type (toxin inhibited with formaldehyde), given in childhood, booster every 10 years. Usually given in combination with diphtheria toxoid and the acellular
• pertussis vaccine (DTaP)

• • When trauma occurs, wound cleaned
• and debrided AND tetanus booster given.

• If would is grossly contaminated, tetanus immune globulin, as well as the toxoid booster should be
• given and penicillin administered.
• Tetanus immune globulin (tetanus antitoxin) is made in humans to avoid serum sickness reactions that occur when antitoxin made in horses is used. The
• administration of both immune globulins and tetanus toxoid (at different sites in the body) is an example of passive-active immunity

-takes 24-48 hours because ingest preformed toxin

- descending weakness and paralysis, including diplopia, dysphagia, and respiratory muscle failure

no fever. Blurred vision, dilated pupils that remain fixed, dry mouth, constipation, abdominal pain.

-flaccid paralysis (weak or absent muscle contractions) occurs, contrasts Tetanospasmin

- pt’s succumb to paralysis and respiratory failure

• Three clinical forms:
• • Wound Botulism: spores contaminate a wound, germinate, and produce toxin at the site (localized infection)followed by systemic spread of toxin
• - associated with drug abuse, especially skin-popping with black tar heroin

• • Infant Botulism
• - organism grow in the gut and produce the toxin there (localized infection) followed by systemic spread of toxin.
• -ingestion of C. botulinum spores (not the vegetative cell, and not preformed toxin)
• -Honey containing the organism is implicated in transmission of this disease
• - infants develop weakness or paralysis and may need respiratory support but usually recover spontaneously; also constipation due to neurotoxin effect on peristalsis, weakened suckling and swallowing, loss of
• head control
• - accounts ½ of the cases of botulism in US

• • Botulism Food poisoning:
• rapid, w/in 24-48 hrs caused by ingestion of preformed toxin; time of symptom onset is slightly delayed following ingestion due to time required to
• reach target tissues of the CNS

• • puncture wounds are more serious than open
• wounds with regard to clostridial infections

• • gram pos rods
• • longer and more deeply staining
• • forms spores
• • one of the most potent toxins known (1 mg of toxin can kill entire family)
• • spores are obligate anaerobes (survive in canned products)
• • Infant: assoc. w/ eating of spores (honey)
• • ferment a multitude of organic compounds and degrade biomaterials

• • widespread in soil, contaminate vegetables and meats.
• foods are canned or vacuum-packed w/out adequate sterilization, spores survive and germinate in
• the anaerobic environment. Toxin is produced w/in the canned food and ingested preformed.

• • Highest risk foods: alkaline vegetables (green beans, peppers, mushrooms), smoked fish.
• • failure to sterilize food during preservation allows spores to survive

• genetic info encoded on bacteriophage and are obtained via lysogenic conversion

• • NO CELL SURFACE COMPONENTS
• have been identified which act as virulence factors

• • Botulinum toxin
• - absorbed from the gut and carried via the
• blood to peripheral cholinergic nerve synapses --> blocks release of Ach causing flaccid paralysis; protease that cleaves the proteins involved in Ach
• release
• - toxin is a polypeptide encoded by lysogenic
• phage
• -8 antigenic types (A,B,E common)
• • spores germinate in anaerobic environment and produce toxin
• • toxin is heat-labile; it’s inactivated by boiling for
• several minutes

Among the most toxic substances known --> 1 microgram is enough!

• • Botox: commercial preparation of exotoxin
• A used to remove wrinkles on the face; minute amounts of the toxin are effective in the tx of certain spasmodic muscle disorders such as torticollis, “writer’s cramp”, and blepharospasm

• • Dx: use antitoxin to detect toxin in pt’s stool, serum, or food
• - organism is usually not cultured

- toxin is demonstrable in uneaten food and the pt’s serum by mouse protection tests. Mice are inoculated with a sample of the clinical specimen and will die unless protected by antitoxin

• • Tx: trivalent antitoxin to A, B, E made in horses (serum sickness occurs in 15% of antiserum
• recipients) given along with respiratory support

wound botulism: debridement and proper wound care, ventilatory care, and ABX intervention in infant botulism: respiratory support and ABX

• • Prevention: proper sterilization of all
• canned and vacuum-packed foods is essential. Food must be adequately cooked to inactivate the toxin. Swollen cans must be discarded (clostridial proteolytic
• enzymes form gas, which swells cans)

G+, SPORE, ANAEROBE

• GAS GANGRENE (WOUND)
• CREPITUS
• ALPHA TOXIN
• SYSTEMIC TOXEMIA (shock & renal failure)
• FOOD POISON (PREFORMED)

• • Gas gangrene (myonecrosis, necrotizing fasciitis)
• - caused by other histotoxic clostridia
• - associated with war wounds, automobile and motorcycle accidents, and septic abortions (endometritis)

• -alpha toxin causes most of the trouble
• - localized infection with systemic toxemia
• -increased vascular permeability, massive hemolysis and bleeding, tissue destruction, hepatic toxicity, myocardial dysfunction (bradycardia, hypotension)

• • pain, edema, and cellulites
• in wound area

• crepitation indicates the presence of gas in tissues

• • jaundice and blood-tinged
• exudates

• shock, renal failure w/in a few days of onset and death can ensue, mortality rates high

• • food poisoning- enterotoxin acts as
• heat liable enterotoxin with superantigen
• properties, causing diarrhea with cramps and some vomiting
• -intoxication due to ingestion of a preformed toxin, often in meet products (beef, chicken, turkey)
• - 8 to 16 hr incubation period, resolves in 24-48 hrs hrs
• -rapid onset (8-24 hrs) of abdominal cramps and watery diarrhea
• -no fever, no nausea or vomiting

• • puncture wounds are more serious than open
• wounds with regard to clostridial infections bc…

• • anaerobic
• • gram pos
• • form spores
• • ferment a multitude of organic compounds and degrade biomaterials à important environmental partners in the biodegradation process, but these enzymes enhance organisms’ invasiveness and
• pathogenicity if infection occurs

• TRNS
• • soil
• • vegetative cells are members of the normal
• flora of the colon and vagina
• • gangrene from contamination of wound w/ soil or feces
• • food poisoning from ingestion of contaminated food; heat-resistant spores survive cookin and germinate. The organisms grow to large #s in reheated foods, especially meat dishes

• • NO CELL SURFACE COMPONENTS
• have been identified which act as virulence factors

• • organisms grow in traumatized tissue (especially muscle)
• • alpha toxin- lecithinase (phospholipase C) that hydrolyzes lecithin (in cell membranes) --> cell lysis, including those of erythrocytes (outer zone of hemolysis), platelets, leukocytes, and endothelial cells

• degredative enzymes produce gas in tissues

• theta toxin (hemolysin)- in double zone hemolysis, theta does inner zone of complete hemolysis, and alpha toxin the outer zone of incomplete hemolysis

• other toxins: hemolysin, DNase, hyluronidase, and collagenase. Causes lysis or destruction of RBCs, DNA, hyaluronic acid, and collage, leading to tissue destruction and necrosis

• • food poisoning, C. perfringens is normal flora in the colon but not in the small bowel. Mode of action of
• this enterotoxin is the same as that of the enterotoxin of S. aureaus (superantigen)

• Dx: Gram stain and anaerobic culture

sugar fermentation rxns and organic acid production.

lecithinase on egg yolk agar (Naegler test -- 3 strips), causing visible precipitation, inhibited by vertical antitoxin strip(specific to alpha toxin)

• - present double zone of hemolysis on
• blood agar

• • Tx: Penicillin G and debridement of the wound
• -hyperbaric O2 tx- in conjunction w/ surgical and conventional anti-microbial txs, provides additional oxygen to body tissues. Inhibits alpha toxin, suppressing growth. Enhances healing by generation of new microscopic blood vessels AND INC ability of phagocytes to kill organisms
• • Prevention: wounds should be cleansed and debrided

Penicillin for prophylaxis, no vaccine

• In food poisoning,
• Dx: not usually done, no assay for the toxin. Large #’s of the organisms can be isolated from uneaten food.

• Tx:
• symptomatic tx is given; no antimicrobial drugs are administered

Prevention: no specific preventive measures; food should be adequately cooked to kill out the organism

G+ ROD, ANAEROBE, SPORE

• • ABX associated Pseudomembranous colitis
• TOXIC MEGACOLON

- most common nosocomial cause of diarrhea (non-bloody). Fever, abdominal cramping.

Diarrhea is in many cases a side effect of many oral ABX

-elaboration of a toxin only after onset of an active infection

• - pseudomembranes are thick, adherent, grayish or yellowish exudates on the mucosa surfaces on the colon of this disease
• - neutrophiles found in stool in ½ of cases

• - Clindamycin as the cause of pseudomembranous colitis, but many ABX are known to cause the disease
• - 2nd and 3rd generation cephalosporins are the
• most common causes bc they are so frequently use; Ampicillin and fluoroquinolones are commonly implicated
• - cancer chemo also predisposes to this diesase

• • toxic megacolon can occur: surgical resection may be necessary
• • puncture wounds are more serious than open wounds

• • anaerobic
• • gram pos rods
• • form spores
• • yellow-white plaques on the colonic mucosa
• • ferment a multitude of organic compounds and degrade biomaterials: important environmental partners in the
• biodegradation process
• • In 2005, a more virulent strain of C. difficile emerged: more severe, causes more recurrences, respondes less well to metronidazole than the previous strain, resistance to quinolones due to the widespread use of quinolones for diarrheal disease, which has
• selected for this new strain

TRNS:

• FECAL-ORAL
• • in the GI tract in approx. 3% of the population and up to 30% of hospitalized pt’s.

• Most ppl are not colonized (ppl who take ABX do not get pseudomembranous colitis)
• • fecal-oral transmission; hands of hospital personnel are important intermediaries

• rarely invades the intestinal mucosa

• • NO CELL SURFACE COMPONENTS
• have been identified which act as virulence factors

• • antibiotics suppress normal flora allowing C. difficile to multiply and produce exotoxin A and B (NOT A-B) --> BOTH glucosylate G protein called Rho GTPase.
• • Toxin A: responsible for clinical disease, causes fluid production/mucosal damage to colon
• • Toxin B: cytotoxic activity, responsible for cytopathic effect (CPE) BY ACTIN DEPOLYMERIZATION

-both inhibit GTPases, inhibiting signal transduction and depolym. of actin: loss of cytoskeletal integrity, apoptosis, and death of enterocytes

-pseudomembranes are result of death of cells

• Dx: detect Toxin B in fecal sample via observed CPE

• 2 tests:
• - ELISA using known Ab to the exotoxins (rapid and less sensitive than the cytotoxicity test)
• - cytotoxicity test: human cells are exposed to the exotoxin in the stool filtrate and the death of the
• cells is observed; more sensitive and specific but requires 24-48 hrs incubation.

• To distinguish btw CPE caused by virus and exotoxins, Ab vs. the exotoxins is used to neutralize the CPE (Toxin B)
• - sigmoidoscopy helps visualize the pseudomembrames

• • Tx: Causative ABX should be withdrawn. Oral
• Metronidazole or Vancomycin should be given and fluids replaced, the former
• preferred bc using Vancomycin may select for Vancomycin-resistant enterococci. In many pt’s, tx doesn’t eradicate the carrier state and repeated episodes of colitis can occur

• • Prevention: no vaccine or preventive drugs.
• ABX should be prescribed only when necessary

G+, NON-SPORE, CLUB SHAPED

• • Diphtheria
• -toxin production and spread following localized infection
• -most prominent sign: pseudomembrane over the tonsils and throat
• -rare in the US
• -fever, sore throat, cervical adenopathy
• - 3 prominent complications:
• 1) extension of the membrane into the larynx and trachea --> airway obstruction
• 2) myocarditis accompanied by arrhythmias and circulatory collapse
• 3) nerve weakness or paralysis, especially of the cranial nerves. Paralysis of the muscles of the soft palate and pharynx --> regurgitation of fluids through the nose. Peripheral neuritis affecting the muscles of the extremities also occurs.

• • Diphtheroids- corynebacteria that do not
• cause diptheria

• G+ ROD
• • facultative anaerobes
• • does not form spores
• • catalase negative
• • club-shaped gram pos rods arranged in V
• or L shape. Thinner on one end than the other.
• BABST-ERNST GRANULES - polymerized polyphosphate (volutin)

PHAGE --> TOXIC GENE

• • rods have a beaded appearance – beads consist of granules of highly polymerized polyphosphate, a storage mechanisms for high-energy phosphate
• bonds.
• -Granules stain metachromitically (dye that stains the rest of the cell blue will stain the granules red)

• TRNS:
• • human are the only natural host
• • reside in URT
• • transmission via respiratory droplets
• • can also infect the skin at the site of preexisting skin lesions

-occurs primarily in the tropics, but can occur worldwide in indigent persons with poor skin hygiene

• • toxin gene is carried by a lysogenic bacteriophage
• (Beta-phage); the DNA of the virus integrates into the
• bacterial chromosome and the toxin is synthezied

• •nontoxigenic strains can cause certain blood infections, endocarditis, septic arthritis,
• osteomyletitis, abscesses

• invasiveness is necessary: must first establish and maintain itself in the throat

• Diphtheria toxin: iron-regulated by chromosomally encoded element known as the diphtheria toxin repressor (DTxR) (in low iron, this element is not active, organism can produce toxin; when elevated, DTxR repressor becomes activated and binds to the toxin gene operator, resulting in the shut down of toxin production by the organisms)

• -ADP-ribosyltransferase: inhibits protein synthesis by
• adding ADP-ribose from NAD to elongation factor (EF2), which is critical to protein synthesis
• -affects all eukaryotic cells regardless of tissue type, NO EFFECT on the analogous factor in prokaryotic cells

• -single polypeptide with 2 domains: 1) B
• (binds) fragment: mediates binding of the toxin to glycoprotein receptors on the cell membrane 2) A (active) fragment: possesses enzymatic activity that cleaves nicotinamide adenine dinucleotide (NAD) and transfers the remaining ADP-ribose to EF-2,
• inactivating it.

• -host cell receptor: heparin-binding
• epidermal growth factor (HB-EGF) is in heart and nerve cells

• • Host response:
• 1) local inflammation in the throat, with a fibrinous exudates that forms the tough, adherent, gray pseudomembrane characteristic of this disease
• 2) Ab that can neutralize exotoxin activity by blocking the interaction of fragment B with the receptors, preventing entry into the cell

• Dx: gram stain requires both isolating the organism and demonstrating toxin production

• - Loffler’s medium, a tellurite
• plate, and blood agar plate. Tellurite plate contains tellurium salt that is reduced and precipitated to elemental tellurium w/in the organism. The typical gray-black color of tellurium in the colony is a
• telltale dx criterion
• -Ab-based gel diffusion precipitin test: performed to document toxin production. PCR assay for the presence of toxin gene can be used.
• -stained w/ Methylene Blue- Babes Ernst polymerized
• metaphosphate granules give a beaded appearance; metachromatic granules (composed of metachromatic volutin)
• -Elek test-immunodiffusion test that identifies the microorganism producing diphtheria exotosin. Agar plate is inoculated horizontally w/ 3 different strains. The top and bottom streaks represent known toxin-producing and toxin non-producing strains, respectively, as controls. The middle streak on the plate represents the patient[s isolate. A paper strip, saturated with commercially available antitoxin, is placed perpendicular across the bacterial streaks. The presence of diphtheria toxin is indicated by
• immunoprecipitation caused by anti-toxin Abs in the filter strip diffusing into the agar and complexing with toxin released by the microorganisms
• - Schick’s test: immune status of a person can be assessed; performed by intradermal injection of 0.1 mL of purified standardized toxin. If pt has no antitoxin, the toxin will cause inflammation at the sites 4-7 days later. If no inflammation occurs, antitoxin is present and the pt is immune. Test is rarely performed in the US, except under special epidemiologic
• circumstances

• • Tx: antitoxin made in horses neutralizes toxin, should be used immediately bc toxin binds rapidly and irreversibly to cells and once bound, cannot be neutralized by antitoxin.
• Neutralizes unbound antitoxin in the blood. Should be tested first for hypersensitivity since it’s made in horses.
• Penicillin G and erythromycin is recommended, inhibiting growth of the organism, reducing toxin production, and decreasing the incidence of chronic carriers.

• • Prevention: toxin vaccine. Diptheria toxoid or DT with inactivated toxin (usually given as a combination of diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine “for whooping cough” – DTaP). Acellular pertussis vaccine used due to adverse reactions. Prepared by tx the exotoxin w/
• formaldehyde, which inactivates the toxic effect but leaves the antigenicity intact (immunogenic but NOT toxgenic). Three doses: 2,4, and 6 months of age
• and booster every 10 yrs. Immunization does not prevent nasopharyngeal carriage of the organism.

• Meningitis and sepsis in newborns

-Pregnant women (especially 3rd trimester due to reduced cell immunity)

-Immunocompromised adults (especially renal transplant pt’s)

• • Infection during pregnancy (transplacental spread): cause abortion, premature delivery, or sepsis during the peripartum period. Newborns infected at the time of delivery can have acute meningitis (dissemination) 1-4 wks later. Bacteria reach the meninges via the bloodstream (bacteremia). Infected mother either is
• asymptomatic or has an influenza like illness.

• In immunocompromised adults: cause sepsis or meningitis

• febrile Gastroenteritis: watery diarrhea, fever, headache, myalgias, and abdominal cramps, little vomiting. Outbreaks usually caused by contaminated dairy products, but undercooked meats such as chicken and hot dogs have also been involved

• • small gram pos rods, arranged in V or L shape
• • aerobic
• • do not form spores
• • facultative intracellular pathogen (can grow both intracellular and extracelullar)

• • exhibits unusual tumbling movement that distinguishes it from the corynebacteria, which are nonmotile.
• •colonies in blood agar: narrow zone of beta-hemolysis that resembles the hemolysis of some streptococci
• • grows well at cold temperatures, so storage of contaminated food in the refrigeratior can increase the risk of gastroenteritis – paradoxical growth is called “cold enhancement”

• •relatively heat resistant and can withstand
• pasteurization process

• distributed worldwide in animals, plants, and soil.

Transmitted to humans primarily by ingestion of unpasteurized milk products (cheese), undercooked meat (delicatessen meats), and raw vegetables; widespread in nature

• • transmission across placenta or by contact during delivery
• • can grow in enterocytes or in M cells of Peyer’s patches, macrophages, and epithelial cells

• ActA RECEPTOR
• LISTEROLYSN O (ph activated in phagosome)

•invasion: uses surface proteins internalins (In1s) --> endocytosis into phagosome (surviving phagosome-lysosome fusion) and E-cadherin on the surface of human cells.

Ability to pass placenta, enter meninges

invasion of GI tract depends on the interaction of internalin and E-cadherin.

• • Listeriolysin O (hemolysin): activated by acid pH of the phagolysosome; allows it to escape from the
• phagosome into the cytoplasm

• • Actin rockets helps it move from cell to cell; a filament of actin that contracts and propels the
• bacteria through the membrane of one human cell into another;

• -Listeria has a receptor (ActA) that binds actin resulting in an actin halo --> rearranges to form a “comet” tail-like structure that appears to propel the listeria toward the surface of the host cell
• -Long filapodia (pseudopodia) form at the surface and contain the listeria; they carry the pathogen outward extending into the next host cell: protects pathogen from Abs and other extracelullar antimicrobial substances.

• Host defense:
• • Cell mediated immunity more important than humoral

• Predisposing factors:
• • suppression of cell-mediated immunity, such as pt’s
• with AIDS, lymphoma, and transplant

•Dx: gram stain, narrow zone B-hemolytsis, confirmed by presence of tumbling motility, which differentiates from nonmotile cornybacteria.

• -gram pos rods resembling dipththeroids
• -formation of gray colonies
• -sugar fermentation tests

•Tx: trimethoprim-sulfamethoxazole. Combinations such as ampicillin and gentamicin or ampicillin and trim-sulfa can also be used.

• -resistant strains are rare
• -tx for gastroenteritis does not require tx

•Prevention: pregnant women and immunocompromised should not ingest unpasteurized milk;

no vaccine.

• Trimethroprim-sulfa given to immunocompromised to prevent Pneumocystis
• pneumonia can also prevent listeriosis

CLOSTRIDIUM TETANI

2 COMPONENT EXOTOXIN (A-B)

TOXEMIA: SPREADS TO CNS

DELAYED: SPORES GERMINATE IN BODY

TAKEN UP AT NMJ: BINDS TO GANGLIOSIDE RECEPTORS

ACTS ON INH RENSHAW CELL INTERNEURONS

PREVENT RELEASE OF GABA GLYCINE

1 ANTIGENIC TYPE (BOTULINUM HAS 8)

HUMANS: A,B,E (8 TOTAL; TETANI ONLY 1)

FOOD POISONING: RAPID (24-48 HRS DUE TO TIME OF TRAVEL TO CNS): INGESTION OF PREFORMED TOXIN

HEAT LABILE

PHAGE DELIVERED

PREVENTS RELEASE OF ACh AT PERIPHERAL SYNAPSES --> FLACID PARALYSIS

INITIAL S/S BILATERAL CN PALSIES (DIALATED PUPILS) AND DYSPHAGIA, CONSTIPATION, DRY MOUTH, ABD PAIN

INFANT INGEST FOOD W/ SPORES --> GI

WOUND BOTULISM

ALSO RELEASED UPON LYSIS

CLOS. PERFRINGES

INGESTION OF PREFORMED TOX IN MEAT: IMMEDIATE, NO FEVER EMESIS OR NAUSEA

HEAT LABILE WITH SUPERANTIGEN QUALITIES (LIKE STAPH)

Lecithinase (phospholipase C) that hydrolyzes lecithin (in cell membranes) --> lysis, including those of erythrocytes (outer zone of hemolysis, INNER ZONE IS THETA TOX), platelets, leukocytes, and endothelial cells

NAEGLER TEST - EGG YOLK

• degradative enzymes produce gas in tissues: CREPITUS

CLOS. PERFRINGES

MINOR HEMOLYTIC TOX

DOUBLE ZONE HEMOLYSIS (INNER ZONE) ON BLOOD AGAR

4 OTHER TOXINS: HEMOLYSIN, DNASE, HYALURONIDASE, COLLAGENASE

CLOS. DIFFICILE

BOTH GLUCOSYL TRANSFERASES ACT ON G PROT RHO GTPase

B ESPECIALLY CAUSES DEPOLYMERIZATION OF ACTIN --> LOSS OF CYTOSKEL INTEGRITY, APOP, AND DEATH OF ENTEROCYTES

FOUND IN STOOL

BACILLUS ANTHRACIS

PREVENTS PHAGO

PLASMID pXO2

BACILLUS ANTHRACIS

ENCODE EF AND LF, BOTH ACTIVE COMPONENTS THAT WORK WITH PA --> ANTHRAX EXOTOXIN

A-B-LIKE STRUCTURE

• •Two enterotoxins:
• - one like cholera (diarrheal): A-B5, ADP-ribosylation OF G PROT --> STIMS adenylate cyclase AND INC cAMP w/in enterocyte. Toxin is fairly heat-labile.

- other like staph (superantigen); STIMS release of IL-1 and IL-2 from macrophages and helper T cells, respectively. Vomiting is due to cytokines from lymphoid cells --> STIMS enteric nervous system to activate vomiting center in the brain. This toxin is fairly heat-resistant and is therefore usually not inactivated by brief cooking. It´s resistant to stomach acid and to enzymes in the stomach and jejunum. There are 6 immunologic types (A-F).

Synthesis is iron-regulated by chromosomally encoded element known as diphtheria toxin repressor (DTxR)

• Low iron --> ACTIVE TOXIN; REPRESSOR not active; elevated, DTxR repressor becomes
• activated and binds operator --> shut down of
• toxin production

• -ADP-ribosyltransferase: inhibits protein synthesis by
• adding ADP-ribose TO (EF2) FROM NAD

-affects all eukaryotic cells regardless of tissue type,

NO EFFECT on analogous factor in prokaryotic cells

• -single polypeptide with 2 domains: 1) B BINDING fragment: mediates binding of toxin to glycoprotein
• receptors on the cell membrane 2) A (active)
• fragment: cleaves nicotinamide NAD and transfers the remaining ADP-ribose to EF-2, inactivating it.

-host cell receptor: heparin-binding epidermal growth factor (HB-EGF) is in heart and nerve cells

LYSOGENIC CONVERSION OF CORYNE. DIPTHERIA

DIPTHERIA TOXIN

SHIGELLA -- IPA (INVASION PLASMID ANTIGEN) (ABX RESISTANCE)

SALMONELLA -- FIMBRIA

SALMONELLA -- TYPHI ABX RESISTANCE

C. TETANI -- TETANOSPASMIN

ANTHRAX -- EXOTOXIN pXO1 (PA, EF, LF)

ANTHRAX -- POLY -D- GLUT CAPSULE (pXO2)

HAEMOPHILUS INFLUENZA -- R-PLASMIDS

PSEUDOMONAS -- PYOCINS (ANTIBAC)

YERSINIA PESTIS - VIRULENCE GENES (YAD, YOPS, FRA, PLA)

EHEC -- SLT (VEROTOX)

V. CHOLERA -- TOXIN (CTX PHAGE)

CLOS. BOTULINUM -- TOXIN

DIPTHERIA -- TOXIN

• SALMONELLA
• SHIGELLA
• YERSINIA
• CAMPYLOBACTER

Gram Pos, oval shaped yeast

• § Pseudohyphae
• § Blood: non-hemolytic w/ few colonies
• § McConkey’s: no growth
• § Very large
• § Saberos-dextrose agar.
• ·
• Serologic testing is rarely helpful

• Chlamydospores:
• Can make Psuedohyphae=constrictions OR hyphae=smooth.

• Vaginitis in immunosuppressed
• ·
• Part of normal flora
• ·
• IV drug abuse
• ·
• Pseudomembrane in white patches/white secretions.
• ·
• Following a course of antibiotics.
• ·
• Children born from mothers w/candida albicans
• develop oral thrush.

Gram-Neg Rod, can see filaments that distinguish it from N.gon

H.aegyptius: X & V (pink eye)

H.ducreyi: X (STD, chancroid)

H.aphrophilus: subacute endocarditis in patients with underlying damage to valves.

Growth factors distinguish species: X factor (heme), V factor (NAD)

Chocolate Agar: enriched e/ X and V. Blood is heated to inactivate nonspecific inhibitors of H.influenzae growth.

Mucoid appearance due to PSC.

~PSC: polyribitol phosphate is antiphagocytic. Though floral infections are non-encapsulated.

• ~Type B most invasive b/c produces proteaseàcan
• colonize mucosal layers.

Endotoxin.

Many types produce beta-lactamase

~Type B was most common cause of meningitis until conjugate vaccine was developed.

• Vx: Originally, purified capsular polysaccharides, but these are TI-2 Ags, so don’t work well in children. Conjugate this w/ diptheria toxoid --> T-cell
• dependent response.

~Epiglotitis: obstructs airway

~Serious sequalae, especially infantile: meningitis

G-neg, small coccobacillary

Non-invasive, only effects humans.

Bordet-Gengou medium: positive medium, pearl-like colonies

• Agglutination w/ specific antiserum or
• fluorescent Ab staining.

PCR very good.

Finding actual bug a problem, easier to find Ab in serum.

Capsule

Filamentous hemagglutinin (Fha): main adhesin

Pertussis toxin (Ptx): responsible for epithelial cell death. A-B toxin.

B binds ciliated resp cells & phagocytic cells.

A binds catalyzes ADP-ribosylation --> inc cAMP--> inhib neutrophil activation. Also resp lymphocytosis inhibits chemokine signaling to bring lymphocytes back. T lymphocyte mitogen.

Adenylate cyclase Exotoxin: affects PMN--> inc cAMP --> disrupts normal ox function but requires CaM

2-Component Reg Sys: @25C, no toxins or virulence factors are produced. Sensor protein, BvgS, phosorylates BvgA --> transcription of toxins/virulence factors.

Tracheal Cytotoxin: fragment of bacterial peptidoglycan, acts w/ endotoxin --> Stim IL-1 --> induce NO --> kills ciliated epithelial cells.

Whooping Cough=decreased ciliary activity

7-10D Incubation

1-2W Catarrhal stage: cold, contagious.

>2W Paroxysmal stage: whoop

Respiratory droplets

Vx: Boostrix=DTaP acellular vaccine w/ 5 Ags.

Recommended for 10-18yo. Inactivated pertussis toxin. Adacel: good for 18-64yo

Erythromycin good choice, though will have little influence course of toxin b/c toxin have already caused damage

Gram-neg that stain faintly, rods

Facultative intracellular bacterium; ribosome-lined vacuoles surrounded by mitochondria.

Flourscent staining of Ag.

Stops endosome-lysosome fusion.

Buffered charcoal yeast extract (BCYE) agar w/ L-cysteine and iron salts.

• Saphrophyte, lives in H2O. Environmental water
• source, water-cooling towers.

CMI most important defense

• Sx:
• hyponatremia; mental confusion, sometimes diarrhea

Legionaire’s Disease AKA Pontiac Fever (less endemic)

Pleomorphic gram-neg rod

Flourscent Ab-staining

• Type A more virulent (America)
• Type B: less virulent (Europe)

• Sx: tularemia: granulomas in lung, liver and spleen
• “Ulceroglandular”

Tick/Deerfly bites.

Extreme pathogenecity

No person-person spread.

• Any for of rabbits associated w/this disease
• and ticks/larvae.

Gram-Neg rod w/bipolar staining (safety pin)

Highly Invasive

Facultative Intracellular: multiples in macrophages

F-1 PS protein capsule, anti-phagocytic capsule.

Endotoxin-relates symptoms

• Exotoxin
• V Ag
• W Ag

• Yops: protease that cleaves signal transductionàtumor,
• inhibits cytokine production Iron-acquisition system.

Extremely virulent

Transmission by fleas (rat flea)

Sx: buboes

• Vx: formalin-killed protects against bubonic
• but not pneumonic plague.

• Urban
• plague: rats

• Sylvatic plague: accidental encounter of wild rodent
• reservoirs.

Small, gram-neg rod (coccobacilli)

Catalase Positive

Ferments glucose and sucrose

Chocolate agar: lg butterfly colonies

Blood agar: lg butterfly colonies

Cat scratch disease in immunocompetent individuals

Bacillary angiomatosis

Sx: Cellulitis, axillary tenderness, lymphadenopathy

Small, gram-neg rod (coccobacilli)

ZOONOTIC

Warthin-Starry silver stain

Urease-positive

Oxidase-positive

Can’t ferment glucose

Sx: bacillary angiomatosis, proliferative, vascular lesions

• Gram-pos, but do not absorb stain b/c of waxy
• coat.

Produce Niacin

Kinyoun’s acid-fast stain w/carbolfuchsin --> mycobacteria are pink

Auramine-rhodamine stain --> flourscent staining --> yellow/orange

Generally, really hard to grow and group really slowly.

• Non-motile
• Non-spore forming
• Non-toxin producing

Night sweats, coughing, gagging, weight loss are VERY typicial of ALL mycobacteria.

Facultative intracellular/obligate anerobe???

• Produce Niacin but NO conversion --> free
• niacin accumulates will react with cyanogen bromide to form yellow-colored compound

Serpentine Cording: if colony is flattened and spread on microscope. B/c of cord factor glycolipid, trehalose 6,6’dimycolate

• Lowenstein-Jensen agar: egg yolk. B/c this is such a rich culture, it will grow MANY bacteria. So, they
• add malachite green dye to kill off the other bacteria.

Nitrate reductase positive

Heat labile catalase positive

Catalase-peroxidase neg

Blood Agar: does NOT grow b/c it’s very fastidious

Auramine-rhodamine flourscent stain: pretty selectively binds mycobacteria (all)

• Hide in macrophage, inhibit: -phagosome/lysosome fusion
• -oxidative burst
• -acidification of phagosome
• -inflam cytokine response
• -MHC:C1 Ag presentation—no CTLs

Mycolic acids: allows bacteria to be acid-fast, very hydrophobic, it is like a shield.

Wax D, part of Freund’s adjuvant

Phosphatides: caseation necrosis

Exportative repetive protein: anti-phagocytic

CordFactor—trehalose dimycolate, this is related to the virulence b/c

Transmitted via resp droplets and is EXTREMELY contagious.

Milliary-stage, when disease disseminates to liver or spleen, creating many “millet seed” lesions.

Can Pasteurize

• Dx: TST: PurProDeriv=mis of mycobacterial
• proteins. (+) test does NOT mean there is active or transmissible infection. Test result of Type 4 (delayed)
• hypersensivity. (+)>15mm induration, less if patient is immunocompromised.

• Granuloma: macro or mono eat pathogenàpresent
• to Th1 cell --> secrete IFN-g, TNF (damage lungs), macros secrete proinfoam cytokines (IL-1, IL-6, IL-2, TNF-a), macros form giant cell, poor
• granuloma=caseous necrosis

• Ghon complex comb of 1)single parenchymal lesion,
• 2)caseation resulting in calcified bronchial lymph node

• Exudative Lesion: acute inflammatory response@initial
• infection.

Scrufola: mycobacterial cervical adenitis=unilateral cervical lymphnode tenderness.

GI TB: swallowing exudate

Oropharyngeal TB: painless ulcer

Renal TB: WBC in urine but no other culture.

Azicomycin affects the mycobacteria’s ability to make mycolic acids. CAT-G encodes for catalast peroxidase that activates Azinomycin.

Tx: isoniazid (some resistant b/c of chromosomal, point mutations), rifampin, pyrazinamide, ethambutol

Facultative intracellular

Produce Niacin --> niacin ribonucleotide

Nitrate-reductase ???.

• Non-motile
• Non-spore forming
• Non-toxin producing

Incubation lasts several years

Not very contagious

Transmissible via RespDrop, via lesions on skin.

Armadillo

• Tuberculoid: CM response good: sml numbers of organism. Primarily CD4 response. Lepromin skin test
• positive. Hypopig macular or plaque=like lesions

Lepromatous: poor CM response but there is lg Th2 response(Il-4,5,6): lg number of organisms. Here, we wouldn’t see good response to lepromin skin test b/c no CM resonse.

Many nodular skin lesions (leonine facies). After therapy, erythema nodosum leprosum (ENL)=CMI being restored.

Produce Niacin --> niacin ribonucleotide

• Niacin negative
• Nitrase red neg.

• Non-motile
• Non-spore forming
• Non-toxin producing

• Primarily in animals though humans can get TB
• from unpasteurized milk. Not very common in US.

Group 3

Produce Niacin --> niacin ribonucleotide

• Produce little or no yellow-orange-pigment,
• irrespective of presence or absence of light (nonchromogens)

• Non-motile
• Non-spore forming
• Non-toxin producing

• Cause clinical disease indistinushible from
• TB. Most common bacteria in AIDS patients w/CD4 <200.

Tx: Clarithromycin.

Rod, smallest free-living organism. No cell wall.

Bact membrane contains cholesterol

Nutrient Agar: colony has “fried egg shape”

• Activates complement. Produces auto-antibodies against brain, lung, liver. This causes agglutination
• of RBC.

Walking Pneumonia

Transmitted via Resp Drop.

• Live in UG tract, sex transmitted or during
• birth

• Sx: bronchopheumonia (only in resp of
• airways, not alveoli)

Tx: resistant to Penicilin b/c no cell wall. Use tetracycline. M.pheumoniae susectipble to erythromycin; M.hominis resistant.