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Mechanisms of Pathogenicity Introduction Entering the Host Penetrating Host Defenses Damaging Host Cells Pathogenicity - Introduction Pathogenicity is the ability of a pathogen to produce disease by overcoming host defenses Virulence is the degree of pathogenicity – Expressed as LD50 (lethal dose necessary to kill 50% of the inoculated hosts) – ID50 is also used (dose necessary to infect 50% of the inoculated hosts) Pathogenicity – Entering Host Route of entry is called Portal of Entry Usual portals include mucous membranes – – – – Conjunctiva (eyes) Respiratory tract Gastrointestinal tract Genitourinary tract Pathogenicity – Entering Host Respiratory most common – Microorganisms are inhaled on moisture droplets or dust particles Genitourinary through mucous membranes and direct contact Gastrointestinal through food, water and contaminated fingers Pathogenicity – Entering Host Most microorganisms cannot penetrate skin but can gain access through hair follicles and sweat ducts Can gain entry through inoculation also called parenteral – insect bites – injections – wounds Penetrating Host Defenses Bacterial Elements that Overcome Host Defenses – – – – Capsules Cell Wall Components Enzymes Cytoskeletal Components Penetrating Host Defenses Capsules – Prevent or reduce phagocytosis – Usually polysaccharide – Examples » Dextran (S. mutans) » Polyglutamic acid (B. anthracsis) Penetrating Host Defenses Cell Wall Components – Adhesins (adhere to complementary receptors on host cells – Fimbriae – interact with membrane glycoproteins especially mannose – Some microbes reproduce only in host cells Penetrating Host Defenses Enzymes – – – – Leukocidins – destroy white blood cells Hemolysins – destroy red blood cells Kinases – digest blood clots Hyaluronidase – digests mucopolysccharides – Collogenase – destroy collogen of connective tissue Penetrating Host Defenses Via Cell Cytoskeleton – Invasins – Cause actin of microfilaments to form basket to carry bacteria into cell – Found in Salmonella Damaging Host Cells Damage by metabolizing and reproducing in hosts Damage by the production of toxins Two major types of toxins – Endotoxins – Exotoxins Damaging Host Cells Exotoxins – Usually from Gram positive bacteria – Usually a secreted protein product – Heat Labile (60 to 80 deg C) – Very toxic – low LD50 – Usually specific for cell type or cell function – Can be neutralized by antibodies – Symptoms usually appear sooner Damaging Host Cells Exotoxins – Examples – Diptheria toxin –stops protein sysnthesis; damages heart and other organs – Cholera toxin – affects intestinal cells; disrups cAMP a cell secondary messenger – Tetnus toxin – affects nerve transmission – Toxic shock –affects T-cells & macrophages – Listeriolysin – pore forming cytotoxin allows cell to escape phagocytic vesicle Damaging Host Cells Endotoxins – Almost exclusively Gram negative – Present in LPS and released with destruction of cell – Heat stable – often can withstand autoclave – Not easily neutralized by antibodies – Produces general effects fever, aches, shock – Much larger LD50 than exotoxins Damaging Host Cells Endotoxins – Examples – Salmonella typhi and typhoic feverincubation period ~ 1 week symptoms due to LPS induced release of cytokines enter blood and multiply in spleen and liver – S. enteriditis & S. typhimurium – food borne gastroenterits – symptoms usually appear within 24 to 48 hours takes longer than with S. aureus exotoxin