1. Overview of Mechanisms of Damage

Toxins
Lytic enzymes: degrade proteins and extracellular matrix to facilitate dissemination
Intracellular growth: protects bacteria from host immune response
Growth outside the normal site of colonization
Overgrowth of bacteria in normal niches: often after antibiotic therapy
Host immune response

2. Toxins - Significance and Mechanisms

Disrupt cell function or kill host cell
Provide access to nutrients sequestered in host cells
Break down epithelial barrier to enable bacterial spread
Act on cell surface or in cytosol
1. Cell surface: form pores in cell membrane, cleave surface proteins, or cross-link TCR and MHC to activate T cells without specificity
A-B toxins: receptor-mediated endocytosis leads to A domain entry into cytosol
Type III effectors: bacteria bind to host cell and inject toxin (syringe complex)

A-B toxin that works through ADP-ribosylation of proteins
B domain binds crypt and villus cells in small intestine
ADP-ribosylates Gs* inhibiting its GTPase activity causing continuous adenylate cyclase activity and increased cAMP levels
1. Decreased Na absorption, increased Cl secretion, and decreased water uptake secondary to osmotic forces
2. Disease is self-limiting and treat with oral rehydration therapy

Forms spores enabling storage for long periods of time and easy aerosolization
Symptoms resemble viral illness
High fatality rate, even with use of antibiotics such as Cipro
Edema toxin (ET) and lethal toxin (LT) share B subunit
1. ET: A subunit increases cAMP leading to cutaneous edema
2. LT: A domain is a metalloproteinase with particular affinity for macrophages that produces systemic shock and death

Flaccid paralysis
B subunit targets peripheral nerves blocking the release of excitatory neurotransmitters

Spastic paralysis
Binds peripheral nerves at neuromuscular junction and prevents the release of
1. Inhibitory neurotransmitters

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