MedMicroTestA

The study and functional changes in cells, tissues, and organs underlying

Changes in the physiological factors that underlie states

• Cytoplasmic membrane
• cell wall
• S-Layer

Virulence, Etiology, Pathogenesis, Morphological changes, Clinical significance

• External to cyto membrane
• = murein+ outer membrane + Brausn lipoprotein

• = cytoplasmic membrane
• Bacterial membranes have hopanoids, not sterols

• Gives cell rigidity
• Consists of alternating units of two modified sugars (NAM & NAG)
• Chains are cross-linked btw NAM units

• Single thick layer - Peptidoglycan
• Teichoic acids
• Lipoteichoic acids
• NO OUTER MEMBRANE

• Multi-layered, complex
• Thin layer peptid- btw 2 lipid bilayers
• No teichoic acids
• Outer membranes (Phospholipid bilayer, LPS, Proteins)
• LPS (Lipid A, Antigen O, Polysaccharide structure)

• Arrangement (Ext to Peptid- or OM, Archea only layer ext)
• Consist of protein subunits (protein/glyco-, tetrahedral/hexagonal)
• Functions (Adhesion, Maintains cell morpholgy, Phage receptor)

• Point of attack for most abundant drugs
• Imparts virulence factors
• Mechanisms of identification for bacteria

FtsZ, MreB, CreS

• Extracellular polymeric material
• Capsule, slime layer
• Functions - Attachment to substrate, host, other cells; Protection of cell from host, desiccation, viruses, toxins

• well-organized, not easily removed, exludes particles
• Streptococcus, Bacillus, N. Meningitdus, Klebsiella

• Diffuse
• Easily removed
• Pseudomonas

• Long thin proties on appendages
• 20nm wide

• Monotrichous - 1 hair
• Amph - both/either
• Lopho - tuft
• Hairy - Salmonella, E. coli

• Shorter than flagella
• Similar structure
• Few/cells (1-10)
• Functions (Vertical transfer)

Conjugation, Transduction, Transformation

• Exporoium (thin) [outer, inner, undercoat]
• Spore coat (thick protein)
• Cortex (peptide-, dipicolonic acid, Ca++)
• Core

• Situated btw outer and inner forespore membranes
• Membranes often continuous with core on electron micrograph
• Peptidoglycan, dipicolinic acid, Ca++

• Dehydrated layered structure allowing suspended animation of bacteria
• Formed inside some gram-positive bacteria
• Resistant to heat, radiation, acids, desiccation, UV
• Contains copy of chromosomes
• Position of spore in cell used for identification
• Produced by Bacillus and Clostridium

• DNA in A form & bound to small acid-soluble proteins (SASP)
• Core cytoplasm only 10 - 25% water, gel-like
• Ca-diplocolinate but no PG
• pH ~ 5.5 - 6.0
• Also has ribosomes

• Vegetative cell - Stage 0 (DNA becomes dense)
• Stage II - Asymmetric cell division
• Stage III - Mother engulfs forespore
• Stage IV - Cortex Forms
• Stage V - Protein coat surrounds forespore
• Stage VI - Completion of coat (Dipicolinate)
• Stage VII - Lysis of mother cell to release dormant spores (Different sigma factors and 100+ genes reqd)

• Microbes able to multiply at site
• no interference with normal function

= Successful attachment of microbe that may cause damage to the body

Process in which host-microbe interaction leads to alteration of structure of function, causing signs and symptoms

• Commensalism
• Mutualism
• Parasitism

• One benefits, others indifferent
• Corynebacterium spp

Both partners benefit, E. coli

• One organism benefits at the expense of another
• Vibrio spp (Necrotizing Fascitis)

• Fetus in utero lives in sterile environment
• Upon vaginal delivery, exposure
• Colonization 24-48 hr post-natal
• Colonization means established growth on/within host

• Prevent attachment of invaders
• Deplete essential nutrients
• Produce antimicrobial substances (Bacteriocins, Produce toxic metabolites)
• Stimulate

Staph epi, Prop acnes,Clos perf, Acinto Cac, Staph a, Carynem spp, Kocuria spp, Fungi (Candida, Malassezia)

• Gram +, pleomorphic branching
• may appear diptheroid
• Most common anaerobic rod found in clinical specimens
• Catalase (+) Positive

• Gram (-), bacilli, pleomorphic - coccobacilli
• may grow in pairs, do not ferment cabs, Do not reduce to nitrates
• Facultative intracellular organisms
• Oxidase (-) Negative
• Some Citrate (+) Positive
• Contaminate resp. therapy equipment, pillows, catheters
• Resistant to many antibiotics (Aminoglycosides + imipenem)

• A. baumannii
• A. calcoaceticus
• A. lwoffi

• Streptococcus mutans, Srtreptococcus Sanguis, Viridans group
• Plaque = biofilm on teeth
• Progression: Strep -> Actinomyces isralli -> Veillonella -> Neissaria, Fusobacteria
• Tooth surface microbes differ from saliva and mucosa due to redox potential

• Nasopharynx - Haemophilus sp
• Anaerobes predominate in oral cavity
• Peptostreptococcus, Bacteroides, Prevotella, Fusobacterium, Treponema, Capnocytophaga, Eikenella

• S. epidermis
• Debate on whether eye has indigenous microbiota or just transients
• Eye may have nasopharynx flora (Viridians, Haemophilus, Neisseria)

• Normally sterile
• Sterility impeded by trauma, iatrogenic methods

Lactobacillus, Streptococcus, Heliobacter pylori

• Anaerobes
• Peptostreptococcus, Prevotella, Candida, Enterococci

bacteroides, Fusobacterium, Peptostreptococcus, Enterococcus, E coli

• Gram (-) anaerobe, non-pigmented, non-motile, capsulated
• Most common anaerobe in GI tract
• Usually not seen in infections above waist
• B. vulgatisB. fragilis
• Most anaerobe in bactericemia, Most common anaerobe in intrabdominal disease, grows in 20% bile

• Usually sterile in both sexes
• Only urethra and vagina colonized
• Lactobacilli
• Staph Epi (catalase pos, coagulasse neg)
• Viridans group
• Fusobacterium - anaerobes
• Candida albicans
• Ureaplasma
• Other Gram (+) anaerobic cocci

• Nonspecific internal defenses
• First line of defense
• Consist of phys barriers, complement, cytokines, inflammations, receptor proteins
• NOT specifically directed to invading agent
• Responses not affected by prior exposure
• Operates constantly
• no memory
• Usually recognizes HOST

• Skin, epithelium
• Physical action
• Fever
• Inflammation
• Phagocytosis Antimicrobial activity
• Changes in Fe+ availability
• Complement
• Toll-like receptors
• Phagosome, Phagolysosome

• Large granular lymphocytes
• No T cells receptors (TCR), immunoglobulin (Ig) molecules, or CD3 on surface
• Destroy tumor cells and cells infected by some viruses
• Sees every cell as target unless it detects a signal from that cell
• Express CD16 receptor
• NK cells look for MHC Class I molecule
• Destroys these cells = Antibody Dependent Cell-mediated Cytotoxicity
• No memory, Thus part of the innate
• NK cells also involve interaction of FasL of NK cell with Fas protein (CD95) on target cell

• Part of Innate System
• Drosophilia
• Recognize PAMPs
• PAMPs bind CD36 or CD14

• LPS - TLR 4
• Flagellin 0 5
• dsRNA - 3
• ssRNA - 8,7
• CpG DNA 9

• Pamps bind to TLR
• Leads to signals sent to activate transcription factors
• Stimulates production of NF-kB (Cytokine Production) and IRF-3 (Stimulates Type 1 IFN)

• 26 proteins; Cascade activation
• Alternate, Classical, Lectin
• Opsonization, Lysis of cell membranes

• Activation on microbial surfaces
• Fc portion of antibody (Ab) binds microbe surface
• Plasmas protein binds mannose on microbe surface glycoproteins

• Antigen specific
• Memory response
• Involved in two lymphocyte types
• Humoral B-ly secrete Ab; Cell-mediated T-ly activate macrophages
• Includes lymphoctyes and antibodies

Cells produce cytokines that support inflammation and cell-mediated responses

• Cells stimulate eosinophils activation
• Assist B ly
• Promote production of IgM & IgG
• support allergic reactions

Antibody response

• TCR (T cell Receptor) interacts with MHC-peptide-Ag-Complex
• PIP2 -> DAG (Protein Kinases)
• Activation of PKC
• Phosphorylation of several proteins
• Activation of various transcription factors including NF-kB
• Genes activated in nucleus

• regulate cellular responses through binging
• Innate adn Adaptive
• Greater then or less then 30 kDa
• Interferon - Isaac and Lindemann
• Purified - Pestka
• 1st Described - Nagano & Kojima
• Stimulate production of C-reactive protein
• CRP forms pentamer, and binds complement C3 to convert it to C3b
• Inflammation triggers increased CRP

• Hematopoietin
• interferon
• Chemokine
• tumor Necrosis

• IL - 1, 2, 4, 6, 10, 12, 23
• TGF - Beta
• TNF - Alpha

• MEN
• Macorphage
• Eosinophil
• Neutrophil

• Attachment
• Ingestion
• Fusion to form phagolysosome
• Killing in Phagolysosome
• Digestion

• Microbe penetrates barrier
• Capillary Dilation (C3a and C5a)
• Cytokine release
• increased Heat and Blood flow
• Edema and Pain
• Diapedesis of leukocytes to injury site

• Rolling adhesion
• tight binding
• diapedesis (squeeze btw endothelial cells)
• Migration

• (2) Heavy chain, Light Chain(Kappa Lambda)
• Variable and constant region

Mu, Delta, Gamma, Epsilon, and Alpha

• membrane-bound glycoproteins
• Process and present Ag by T-ly
• Self and non-self
• Highly polymorphic gene loci
• Located on chrom 6

Found on all human cells except RBCs

• Found on macrophages, dendritic cells
• Present Ag to Naive T cells, B cell

• cell-mediated (Th1 -> IFN-y, IL-2, TNF)
• IL-2 & IFN activate NK and CD16 receptor
• Cytotoxic T ly then specifically kill infected cells
• Abs neutralize Viruses
• slgA prevents viral attachment (stimulate complement)
• Innate responds to interferons

• dsRNA detected by Toll-like cell receptors
• Induce IFN-alpha and beta
• Activates 2' - 5' Oligoadenylate synthase
• Causes activation of RNAase L

• Ab neutralizes toxins
• C' lyses bacteria
• Ab + C' split C3b - Causing opsonization
• C3a & C5a causes mast cells to degranulate
• macrophage & neutrophil chemotaxis - proteins (toxins0

• Humoral Component (IgE, IgG)
• Cell-mediated component (ADCC) (Cytokines - IL-4,5,3)

• Innate Immunity (Phagocytosis) (Alt & Lectin pathways of C')
• Cell mediated (T cells)

• Stimulation of immune response t challenge with immunogen
• Natural through disease
• Admin by health care worker (Artificial)

• Transfer of performed Ab to recipient
• Given for post-exposure prophylaxis
• Poisonous snake and insect bites
• Risk of type 3 hypersensitivity

• Includes IgG fraction from plasma of donors
• Natural across placenta
• Injection of purified Ab or serum
• Rapid temporary protection

• Botulism
• Tetanus
• Diptheria
• Hepatitis A &B
• Measles
• Rabies

• Immediate Hypersensitivity
• Systemic Anaphylaxis

• Ab-mediated disease
• ADCC
• Cytotoxic cells with Fc receptors to Ab on target
• Transfusions (Hemolytic disease of the newborn) (Drug induced hemolytic anemia)

• Immune mediated
• Ags in excess
• Results in large and small Ag-Ab complexes
• Small IgG aggregates from immune responses dont fix C'

• T cell mediated Ag must be present in context of a MHC class II molecule
• Activated T cells are CD4+TH1 subtype
• T(DTH) is a subset of TH1
• MACs are recruited
• Granulomas

• Tuberculosis - mycobacterim tubercolsis
• Leprosy - mycobacterium lepra
• Schistosmiasis
• Sarcoidosis
• Crohn Disease

• Live but not pathogenic
• Trigger cell mediated response
• Gives herd immunity

• Whole Agent
• Subunit Both require booster doses
• no Herd immunity

MMR, Oral Sabin polio, VZV, Tellow Fever, BCG, Francisella

• Result in undetectable diseases
• Long-lasting immunity
• Cannot cause disease

• Not life long
• Humoral, not cell mediated
• No local IgA response
• Requires booster shots
• Large doses

• Toxoid
• Killed
• Capsule protein subunit usually given with adjuvant

• Alum
• Cell wall components
• Fruends Complete

• Killed
• subunit
• Peptide/polysaccharide
• Toxoid

Anthrax, Cholera, Salk polio, Pertussis, Rabies, Influenza

hep B

• HiB,
• Pneumococcus
• Meninggococcus
• HPV

• Diphtheria
• Tetanus

• Women 9-26 y/o before sexual activity
• HPV serotypes 6, 11, 16, 18
• Protein subunits produced from gen-engineered microbe

HIV, Herpes, Syphilus, Malaria, Cold Viruses, Hep C, Strep pyro, Flu

• Cell wall synthesis (PEP-, Mycolic acid)
• 30s and 50s ribosomes
• Involves metabolites not seen in eukaryotes

• Inhibit Penicillin-binding proteins
• PBPs can no longer catalyze transpeptidase reaction
• Weakened cell wall
• Vanco- binds terminal D-ala-D-ala of pentapeptides
• Cross link btw NAM

• Differ by R groups attached to Beta-lactam Ring
• Pen - 1 R group
• Ceph - 2R groups

Block the initiation of translocation and causes the misreading of mRNA

Blocs attachment of tRNA to the ribosome

Each interferes with a distinct step of protein synthesis

Prevent the continuation of protein synthesis

Prevents peptide bonds from being formed

Prevents the continuation of protein synthesis

Interfere with the initiation of protein synthesis

• Decrease uptake (Alter membrane Perm)
• Drug-activating enzymes (Penicillinase)
• modify drug targets
• Increase export (Efflux pumps)
• Horizontal s Vertical Evolution (qnrA and qnrB)

Competitive inhibitor of para-aminobenzoate

Inhibits dihydrofolate reductase

Lowest conc of drugs that prevents growth of organism in vitro

Lowest concentration that kills 99.9% bacteria

• Recently approved in US, Europe, UK
• Potent vs Tet-R bacteria
• Broad spectrum, Bacteriostatic, IV use
• More resitant vs ribosomal protection and active efflux
• use vs intra-abdominal and soft tissue infections
• use for MRSA, Pen-R Pneumococcus, VRE

Interact at 50 ribo subunit in PTC at A and P sites

• Lipopeptide (Sim to Glycopep- such as vanc-)
• Use vs Gm+ cocci (Enodcarditis-right of heart, MRSA)

Doripenems (Phase III) - Pseudomonas

Ceftobiprole (PhaseIII) - PBP2a in MRSA

Three Agents for treating complicated skin / skin structure infections (cSSSI)

iclapri (Phase III) - csSSSI