Microbial Mechanisms of Pathogenicity Chapter 15 Microbial Mechanisms of Pathogenicity

Microbial Mechanisms of Pathogenicity Pathogenicity The ability to cause disease Virulence The extent of pathogenicity

Portals of Entry Mucous membranes Skin Parenteral route

Numbers of Invading Microbes ID50: Infectious dose for 50% of the test population LD50: Lethal dose (of a toxin) for 50% of the test population

Bacillus anthracis Portal of entry ID50 Skin 10-50 endospores Inhalation 10,000-20,000 endospores Ingestion 250,000-1,000,000 endospores

Adherence Adhesions/ligands bind to receptors on host cells Glycocalyx Streptococcus mutans Fimbriae Escherichia coli M protein Streptococcus pyogenes Opa protein Neisseria gonorrhoeae Tapered end Treponema pallidum

Penetration into the Host Cell Capsule Components of cell wall Enzymes: leukocidin, hemolysin Penetration into the host cell cytoskeleton Figure 15.2

Enzymes Coagulase Coagulate blood Kinases Digest fibrin clots Hyaluronidase Hydrolyses hyaluronic acid Collagenase Hydrolyzes collagen IgA proteases Destroy IgA antibodies Siderophores Take iron from host iron- binding proteins Antigenic variation Alter surface proteins

How Bacterial pathogens damage host cell Direct damage Toxins

Toxins Toxin Substances that contribute to pathogenicity Toxigenicity Ability to produce a toxin Toxemia Presence of toxin the host's blood Toxoid Inactivated toxin used in a vaccine Antitoxin Antibodies against a specific toxin

By-products of growing cell Exotoxin Neurotoxin Cytotoxin Enterotoxin Source Mostly Gram + Metabolic product By-products of growing cell Chemistry Protein Fever? No Neutralized by antitoxin Yes LD50 Small

Exotoxins Superantigens or type I toxins Cause an intense immune response due to release of cytokines from host cells Fever, nausea, vomiting, diarrhea, shock, death

Exotoxins Membrane-disrupting toxins or type II toxins Lyse host’s cells by: Making protein channels in the plasma membrane (e.g., leukocidins, hemolysins) Disrupting phospholipid bilayer

Exotoxins A-B toxins or type III toxins Figure 15.5

Exotoxins Exotoxin Lysogenic conversion • Corynebacterium diphtheriae A-B toxin. Inhibits protein synthesis. + • Streptococcus pyogenes Membrane-disrupting. Erythrogenic. • Clostridium botulinum A-B toxin. Neurotoxin • C. tetani • Vibrio cholerae A-B toxin. Enterotoxin • Staphylococcus aureus Superantigen. Enterotoxin.

Exotoxins Figure 15.4a

Endotoxin Figure 15.4b

Endotoxins Figure 15.6

Endotoxins Source Gram– Metabolic product Present in LPS of outer membrane Chemistry Lipid Fever? Yes Neutralized by antitoxin No LD50 Relatively large

Cytopathic Effects of Viruses Table 15.4

Pathogenic Properties of Fungi Fungal waste products may cause symptoms Chronic infections provoke an allergic response Tichothecene: toxins inhibit protein synthesis Headache, chills, sever nausea, vomiting, visual disturbance Fusarium Proteases Candida albicans, Trichophyton Capsule prevents phagocytosis Cryptococcus neoformans Ergot toxin: hallucination, gangrene of limbs Claviceps purpurea

Pathogenic Properties of Fungi Aflatoxin: mutagenic toxin Aspergillus flavus Mycotoxins Neurotoxins: Phalloidin, amanitin Amanita phalloides

Pathogenic Properties of Protozoa Presence of protozoa Protozoan waste products may cause symptoms Avoid host defenses by Growing in phagocytes: Toxoplasma Antigenic variation: Trypanosoma

Pathogenic Properties of Helminths Presence of parasite interferes with host function Parasite's metabolic waste can cause symptoms

Pathogenic Properties of Algae Neurotoxins produced by dinoflagellates Saxitoxin Paralytic shellfish poisoning

Portals of Exit Respiratory tract Coughing, sneezing Gastrointestinal tract Feces, saliva Genitourinary tract Urine, vaginal secretions Skin Blood Biting arthropods, needles/syringes

Mechanisms of Pathogenicity Figure 15.9