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 fever-incubation 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