• affected tissue or organ
• host factors
• inoculum size
• virulence of bacteria

1. entry into body
2. adhesion
3. multiplication
4. colonization
5. invasion and spread

• skin
• mucus
• ciliated epithelium
• antibacterial secretions

• passive
  • inhalation
  • ingestion of contaminated food/water
• penetration
  • active penetration (receptor mediated)
  • cell mediated
  • trauma
  • arthopod bites
  • sexual transmission

• ability to adhere
• specific growth requirements
• defects in host defense mechanism
• presence of virulence factors (VF's)

• adhesin molecule (VF)
• host cell receptor

• adhesins are usually lectins
  • proteins that bind sugars usually located at the tip of the pili
• some adhesins are on the bacterial cell surfaces
  • ex: invasins that recognize host cell integrins

• biofilms
• slime
• capsules

• bacteria must multiply for symptoms to appear
  • multiplication
  • overcome host defenses

BACTERIA CAN ONLY COLONIZE AT SITES THAT MEET THEIR GROWTH REQUIREMNTS!!!!

• mediated by
  • presence of adhesins that recognize host receptors in proper environment
• colonization of sites by normal flora helps prevent colonization of new species, but
  • pathogens not controlled by competition in sterile site

• bacteria compete with lactoferrin and transferrin for iron
  • aka both host and bacteria have high affinity iron binding proteins

• live on cell surface
• cross epithelium and remain local
• travel to systemic sites

• function- break down host defenses
• comp.- usually enzymes
• mechanism of action
  • act locally to damage host cells, promote growth and spread of bacteria
  • may be part of disease pathology

• spreading factors
  • collagenases
  • hyaluronidases
  • neuroaminidases
  • staphylo-/strepto-kinases
• hemolysins and leucocidins
  • pore forming proteins
  • phospholipases
  • lecithinases
• coagulases
• extracellular digestive enzymes
• locally acting toxins
• endocytosis inducers

• evolved from nonrelated nonpathogenic bacteria by acquiring large blocks of DNA containing VF's
  • large proportion of VF's on mobile DNA can be spread via:
    • conjugation
    • transformation
    • transduction

• contents
  • gene clusters encoding adhesins, toxins, other VF's
  • maybe flanked by inverted repeats or insertion sequences
  • often encodes a virulence process requiring coordinated expression on several genes
• mechanism of activation- may be turned on by a single stimulus
• origins
  • formly a mobile DNA
  • not found in related nonpathogenic organisms

• components
  • ATP binding cassete (ABC) transporter
  • outer membrane protein (OMP)
  • membrane fusion protein (MFP)
• Energy from ATP hydrolysis

• found in gram negative bacteria
• aka injectisome
  • origin
    • common evolutionary origin with flagellum
  • function
    • deliver effector molecules across cell and host membranes
    • modulate host cell immune and defense responses
  • encoded on pathogenicity island
  • considerable divergence and specialization between species

• function- able to transfer nucleic acids as well as proteins (unique)
• found in gram positive and gram negative bacteria
• energy from ATP hydrolysis
• widespread (VirB1 is only common protein)

• T5aSS
  • transport proteins with N terminal passenger domain and conserved C terminal domain
• T5bSS
  • secrete protein pairs
• T5cSS
  • secrete trimeric proteins

• adhesins
• toxins
• proteases
• cytolysins

• needed in:
  • Vibrio choleral
  • Edwardsiella tarda
  • P aeruginosa
  • Francisella tularensis
• encoed on pathogenicity island
• injectisome similar to T3SS
• not well characterized

• located in gram positive bacteria with mycomembrane
  • cell wall heavily modified with lipid
• not well characterized
• encoded on PI
• required by:
  • mycobacterium TB
  • S. aureus (no mycomembrane)

• phagocytosis following opsinization by complement or Ab

• avoid contact with phagocyte
• inhibit engulfment
• survive inside phagocyte
• kill phagocyte
• avoid the immune response

• go where they dont go
• limit inflammation
• inhibit phagocyte chemotaxis
• camouflage with host molecules

• polysaccharide capsule
• M protein and fimbriae (ex: group A strep)
• surface slime (P. aeruginosa)
• O antigen of LPS
• protein A (S aureus)
• depolymerize actin to prevent engulfment (ex: Yersinia)

• inhibit phagosome-lysosome fusion
  • ex: Salmonella, Mycobacteria, Legionella, Chlamydiae
• resistance to lysosomal enzymes
  • ex: B anthracis, TB, S aureas
• escape from phagosome before fusion
  • ex: Rickettsia

• streptolysin and leucocidin (staph) bind neutrophil membrane and cause degranulation
• exotoxin A from P. aeruginosa
• most intracellular pathogens eventally kill the cell

• tolerance
• antigenic disguise (bacteria cover selves with host molecules)
• immunosuppression (leprosy, TB)
• intracellular habitat
• induce non-neutralizing Ab
• nonspecific T cell response induced by superAg of strep
• absorption of Ab's by soluble factors released by bacteria
• antigenic variation (change antigen ex: fimbriae switching)
• change antigens at the population level
  • serotypes expressing different Ag's

• exotoxins
• AB toxins

• function- major determinants of virulence
• def.- species specific soluble proteins actively released
• seen in gram negative and gram positve bacteria
• mechanism of action
  • highly potent and specific modes of action
  • may attack specific pathway or cause non cell death

• detoxified toxins that retain antigenicity and immunizing capacity

• subunit A- responsible for biological activity
  • activated following release of subunit B
• subunit B- binds to host receptor and initiate transfer of subunit A across the membrane

• cholera
• diptheria
• botulism
• tetanus
• anthrax

1. pore formed by B subunit
2. receptor mediated uptake

• cell lysis via:
  • hemolysins
  • phospholipases
  • pore forming toxins
• ADP ribosylation of host protein
  • leads to inactivation of host protein

• affects normal cell function without killing the cell

• Diptheria toxins
  • ADP ribosylation of EF-2, interfering with protein syn., leading to cell death
  • similar mech. seen in P. aeruginosa
• Cholera toxin
  • ADP ribosylation of Gs, causing continuous syn. of cAMP, block sodium uptake, secrete chloride, and water follows with electrolytes
  • similar mechanism in pertussis toxin and enterotoxins (ex: E coli)

• two different subuints share single B unit
  • A: lethal factor (LF) and edema factor (EF)
  • B: protective antigen (PA)
• PA binds receptor, cleaved by proteases, creating a binding site for LF or EF

• LF (protease)
  • if low- inhibit proinflam. cytokines, causing immunosuppression
  • if high- kill macrophages, causing massive inflammatory response and shock
• EF (adenylate cyclase)- results in immunosuppresion

• toxin blocks depolarization
• lead to flaccid paralysis

• blocks inhibitory receptors at presynaptic bulb
• cause spastic paralysis

• anthrax
• tetanus
• E coli enterotoxin

botulism

diphtheria

Shiga-like

• Bordetella AC toxin
• cholera
• exotoxin A
• pertussis
• Shiga

• found in LPS from gram negative bacteria
• characteristics
  • less potent and less specific than exotoxins
  • not enzymes, heat stable
  • strongly antigenics
• structurally, remain associated with cell wall until cell death or destruction

1. death of gram negative bacteria cause release of endotoxin
2. binding of endotoxin to macrophages and release of cytokines
3. binding of endotoxin and IL-8 to neutrophils causes release of toxic oxygen radicalse and proteases

• damage caused by host response to pathogen, not pathogen directly
• tissue damage from toxic factors released from infiltrating lymphocyts, macrophages, neutrophils
• continuously generated antigens released from viable bacteria cause chronic immune stimulation and immunopathology