MCDB 132 1

• 1. AB toxins
• 2. Membrane disrupting toxins
• 3. Super Antigens

• Diphtheria
• Botulism
• Tetanus

• Clostridium Perfringens
• Gas gang green
• food poision via CPE

staphlococcus Aureus ( TSS)

Streptococcus Pyogenes ( Tss Like ) MORE DEADLY

• spres found in soil, get into food, bacteria grows
• bacteria releases BoNT into the blood stream
• BoNT targets the peripheral neurons ( NOT CNS)
• Effect: Flaccid Paralysis

• Similar to alcohol consumption
• - slurred speech
• -double vision
• -vomiting
• - Respiratory/ heart failure
• ( symptoms start happening 4-6 hrs after ingestion)

• BoNT by the Gram + bacteria Clostridium Botulinium
• - can be food borne
• - colonization
• a. wound botulisim
• b. baby botulism

• The bacteria that causes botulism
• - gram +
• - motile
• - anerobic
• - baccilli : rod shaped
• - spore forming
• - Creates an AB type exotoxin

• spores found in bee honey
• when spores are ingested
• the bacteria actually colonizes the GI tract due to low stomach acid and low natural microflora
• BoNT is produced
• BoNT gets into the Blood stream
• Targets Peripheral Neurons ( NOT CNS)
• = Flaccid Paralysis
• same symptoms as Food borne botulism

• Spores are found in the mud / dirt
• happens during war time when soldiers are covered in mud and hurt
• the spores get into the wound
• since it is a wound o2 is usualy limited and runs out quickly creating an anerobic environment
• bacteria colonizes
• produces BoNT, it enters into the BS
• ! same symptoms as Food borne and Baby botulism

• Put person on a ventilator ( due to respiratory failure)
• Give antibiotics to prevent FURTHER damage done by the neurotoxin

• Type B is an AB exotoxin like botulism
• From bacteria Clostridium Tetani
• C. Tetani produces TeNT

• Type A is a Membrane Disrupting Toxin
• From bacteria Clostridium Perfringens
• C. Perfringens produces CPE ( C. Per. Enterotoxin)

• Gram +
• Anerobe
• Motile
• Baccilli ( rods)
• Causes Tetanus
• Spastic Paralysis
• TeNT: Blocks Gamma Butyric Acid ( an NT inhibitor)

An exotoxin that acts specifically on the Intestinal Mucus

Gas Gang green

• ex. St Patty's Meat
• Membrane disrupting toxin
• spores get into food
• food cools and spores germinate
• Bugs get ingested, colonize GI tract
• Make toxin CPE
• 8-16 hrs after ingestion
• Symptoms:
• Intestingal discomfort ( gas)
• Diarrhea
• Cramping

• Toxic Shock Syndrom
• ex Tampons
• Super Antigen
• caused by : Staphylococcus Aureus (toxin TSST 1) ,
• Staph is : Aerobic, non-motile, coccus

• effects men and women
• caused by Streptococcus pyogenes
• aerobic, non motile, coccus
• *Bugs actually live in BLOOD = more deadly 30% death rate

• *Non specific T cell stimulation
• SA binds directly on MHC II which then binds to a T cell receptor
• This is an efficient binding, and will stimulate 1/5 T cells ( vs 1/ 1000)
• *NO antigen recognition
• T cells now release high levels if IL 2 --> cytokine storm
• SHOCK

Kills bacteria

• Slows down bacteria
• helps immune system combat the slowed down bacteria

• Cell wall
• Protein Synthesis
• DNA/ RNA replicaiton
• Essential Co factors

• *Humans don't have cell wall
• ex. Penicillin : disrupts cell wall of a broad spectrum of bacteria ( gram +/-)
• ex.vancomycin : inhibits cell wall synthesis in gram + ( can't get pass membrane of Gram -

• *bacterial protein synthesis is different from outs, not the same enzymes
• ex. Tetracycline :Binds to bacteria Ribosomes and prevent Translation = no proteins
• also : Kanamycin, Azithromycin

• ex Ciprofluxacin: treats anthrax , inhibits Gyrase in DNA replication
• good for INTRAcellular pathogens

• essential co factor : Folate
• ex. Trimethoprim, Sulfamethoxale : inhibit steps in folate production of bacteria.

• Mutations
• Enzymatic inactivation of drugs
• Efflux
• Modification of Drugs' Target

• Binds to Bacterial Ribosomes
• Stops translations
• No protein synthesis

• Binds to bact Ribosomes
• Stops transltions
• No protein synthesis

• Binds to Bact Ribosome
• No translation
• No protein

• Stops Gyrase
• DNA/ RNA replication
• Good for intracellular pathogens (endogenous antigen)

Disrupts Folate production

Disrupts Folate production in Bacter

• Good for Gram positive Bacteria
• A Cell wall synthesis

• Gram - : get mutations in outer membrane so that drugs can NOT get in
• -ex. mutations in the porforins, it would limit the drugs ability to get it

• Bacteria produces enzymes that degrade/ inactivate the drugs
• ex. Penicillin resistant bugs create Beta - Lactamase which cleaves the Beta -lactam part of penicillin = inactive

ex. Kanamycin res. bugs enzymatically modifies periplasm so that it decreases drug transport

Drug functions properly, finds but, binds to target, gets inside the bug , but the bug just pumps out the toxins.

Bacteria modifies itself so that the drugs can NOT bind

• ex. Penicilllin res. Bact make Beta- lactamase, and so we will give penicillin + a Beta lactamase inhibitor ( complex called augmentin)
• Clavulonic acid = beta lactamase inhibitor

• caused corynebacterium diphtheriae
• "the strangler"
• Highly fatal
• Killed George Washington
• Iditarod Sled Dog Race
• Serum sickness
• Humans are the only reservoire
• 1 molecule of toxin kils 1 cell

• Bacteria that causes Diphtheria
• Gram +
• Facultative anerobe
• non motile
• Club shaped

• aerosoles are inhaled from an infected person
• bacterial colonization of the throat
• Throat becomes necrotic
• Toxin is AB toxin; DT toxin enhances colonization
• Fibrin network begins in leak plasma membrane
• Adherant membrane

• Difficulty Breathing and swallowing
• bacteria stays in throat
• Heart failure due to toxin getting into the blood and targeting the peripheral nerves

• AB toxin
• A: Works by inactivating EF-II and stops translation/ cant make proteins by ADP RibosylationB: Targets the HB-EGF receptor (Heprin binding -epidermal growth factor) on MANY cells like Heart, Respiratory, + many organs

• ADP ribosylation: ( of host cells) transfers ADP ribose from NAD to EF II
• rxn: NAD + EF II ----> Nicatinamid + EF II-ADP riboxyl

• Now made with a Toxoid
• - no toxin, just illicits an immune response
• -Active part ( A) is inactivated with Formaldehyde DT-AB
• Illicits an IgG Ab response, if you have this Ab then you will be protected from toxin

• Causes by the Anti-toxin made with Horse antibodies
• -people were fine if given the toxin once
• -but when given twice the horse proteins would complex with our antibodies which would cause an even more severe response by immune

• Diphtheria , Tetanus, P
• Diphtheria: Corynebacterium diphtheriae
• Tetanus: Clostridium tetani , Clostridium perfringens
• P: whooping cough by bortatella Pertussis

• More tetanus than diphtheria/ whooping
• high school aged children in the US

• there is no 100% efficacy
• some people might not develope Ab to the toxin, but are still protected via
• Herd Immunity: for non-responders who don't have Ab and are safe because the responders are vaccinated and so there is noone to pass it to the non responders.

• use Toxoid of Diphtheria and to illicit immune reaction to toxins that don't illicit immune response
• ex. HIB vaccine against the haemophilous influenza type B
• Haemophilous influenza causes Infant Menegitis
• --> by Covalently linking the CHO capsule to the Diphtheria Toxoid to illicit ( MHC II and T cell response)

• Gram NEGATIVE -, Rod, Capsular Bacteria
• Respiratory Pathogen ( of the upper respiratory tract)
• Causes infant menegitis
• Pneumonia ( thats why they thought it was an influenza)
• Highly lethal due to infants Tcell Independent

Today:Covalently link the Diphtheria toxoid to the Haemophilous Influenza Capsule = immune system process it like a protein with ( MHC II and T cells reponse)

Use the DT-A ( activity fragment without the toxic B fragment attach to the B fragment of the cell you want to target. Ie B frag specific for a cancer cell.

"Magic Bullets"

Kill Cancer cells/ Virually infected cells / w.e. certain cell type you want to kill

• Yersinia Entercolitia : Plague like
• Yersinia Pestis: Plague

• Gram -, rod shaped
• Motile at 25 degree Cel, non motile at 37 degree Cel
• YST : yersinia, heat-Stable enteroToxin
• Plague- Like bacteria but only causes Food Poisoning = Gastroenteritis

• Pathogenesis: Food/ water, ingested, replicates in the mesenteric lymph ( drains into the intestines)
• Found in food/ water sources
• Symptoms: Abdominal pain ( inflammation)

Seems like inflammed appendix

• Gram NEGATIVE (-)
• Rod shaped
• Facultative anerobe
• Capsular bug
• Likes to live with RODENTS
• Causes: Bubonic Plague, Septicimia Plague, Pneumonic Plague, Black Death
• Principally and extracellular Pathogen
• Virulent Plasmids : pPla, pFra + 1 non virulent pYV

• 1. bubonic Plague
• 2. Septicimia Plague
• 3.Pneumonic Plague
• 4. Black death

• Flea bites/ direct contact with an infected rodent
• Pathogen proliferate/ clump in the flea gut
• Clump starves the flea, and needs to Regurgitate to feed again = ravenous fleas
• Bites you and injects the Bacteria into your BLOOD stream, Get into your LYMPH nodes
• Lymph nodes become, HOTswollenHemmorrhatic = Black Bubos ( swellings)
• * swelling in the groin is very common

• Bacteria is in the Lymph nodes and now enters the Blood stream
• Liver, spleen, lungs ( septic)
• when in lungs , you get pnumonia and can start to exhale infectious aerosoles

• after it infects your blood and gets into your lungs, the bacteria changes
• it can now be exhaled and transfered to other humans ( Human - human aerosole transmission)

• via bubonic, septicimia, or pneumonic plague
• VERY Black Extremities
• Hemmoratic changes in the skin ( via DIC .. causes lots of clotting and necrotic tissue proliferate and get black fingers toes etc)
• Septic Shock

• Main two are on Plasmids
• pPla : encodes plaminogen activator protease ( pla protease) = disrupts blood coagulation ( so that the bug can build its house and move around.
• Enzyme works best at ~ 37 Deg Cel ( warmer like places near equator)
• Degrades C3B and C5A, allows it to live in the BLOOD

pFra : (fraction 1 capsule) = Antiphaocytic, phospholipase D ( promotes flea colonization)

* two plasmids only found on yersinia pestis not yersinia entercolitica

• found in ALL Yersinia
• pYV ( yersinia virulence)
• pYV encodes a TYSS -3 : TYpe 3 Secretion System
• TYSS 3 is a molecular syringe that will secrete toxin upon CONTACT
• Toxin: YOPS ( inhibit phagocytosis, and causes macrophage apoptosis)

• from yersinia pestis
• on a Plasmid, is a Protease
• Cleaves blood Clots + Disrupts complement activation ( via degrades C3A and C5A)

• From Yersinia Pestis ( Black death/ plague)
• Phospholipase D : Promotes Flea colonization
• Anti-Phagocytic

• Caused by corynebacterium diphtherae
• Respiratory infection
• Adherant pseudo-membrane
• ADP- ribosylation of EF II( stops protein synthesis disrupt Translation)
• Binds to HH-EGF receptor
• AB toxin
• Serum Sickness
• George washington, Iditarod

• Symptoms:
• Swollen neck/ Bull neck
• Hard time swallowing ( due to adherent pseudo mem)

• Gram +
• Aeresol infection --> bugs colonize throat
• Facultative Anerobic ( likes aerobic)
• causes Diphteria " strangler "

• IMMUNOTOXIN:A portion often used to induce Immune response for other disease/ infections in cancer cells
• Toxoid Carrier Vaccines
• linke
• ex. for Haemophilous infuenzae Type B: CHO bug, can't make Ab, Need the immune response of Diphteria, HIB vaccine does this, so that our body processes the CHO like a protein

• 1. Anti-bodies have already seen that pathogen ( IgG)
• 2. Ab (Fv portion) binds to the Antigen on the Bug surface
• 3. C1 binds to the Ab and cleaves C2 and C4
• C2-C4 --> makes C3 convertase

• Complement component C3B* Binds directly to the Bacterial Surface
• C3B + BP ( blood protein) --> C5 Convertase

• Surgar binding Leptin ( mannose) binds to mannose on Bacterial surface
• C1 binds to Leptin, C2 C4 --> C3 convertase

• Protein factor H binds to C3B stopping C3B function because it is A KEY player
• Then Protein Factor I Destroys C3B

• Membrane Attack complex
• of C5B +C6-C9
• Binds to the membranes of Gram - and KILLS them
• ****however this is NOT the main function of Complement