Microbial Mechanisms of Pathogenicity Virulence is the degree

Microbial Mechanisms of Pathogenicity

• Virulence is the degree of pathogenicity of an organism. • Pathogenicity, Ability to cause disease.

Portals of entry are usually constant for a microbe • Mucous membranes of conjunctiva, respiratory, gut and genitals • Inhalation of dust and moisture particles to lungs – This is the most common entryway • Skin is hard to penetrate – Most enter through hair follicles and sweat ducts – Some fungi may attach to skin cells.

• Microbes gain access to systemic system through – Bites – Injections – Wounds – Called parenteral rout

Preferred Portal of entry • Most cause infection only when they use a specific portal of entry • Example – Yersinia pestis by a number of portals – Streptococcus pneumoniae respiratory tract – Vibrio cholerae gut – Neisseria gonorrhoeae genitals – Clostridium perfringes parenteral

Lethal and infectious doses, the number of invaders determines what the outcome may be • LD 50 # to kill 50% of inoculated individuals • ID 50 # to cause infection in 50% • Is basically a method to compare relative toxicities or conditions

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

Adherence • In order to get into a host the bacteria must stick to it. • Surface projections (ligands) adhere to receptors on host cells. • Mostly on structures called fimbriae • The sugar mannose is the most common receptor.

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

How Bacteria escape programmed host defenses • Capsules are extracellular glycocalyx material that surrounds the cell. Prevent recognition of the bacterial cell. Streptococcus pneumoniae • Cell wall components may also resist recognition and phagocytosis

Enzymes that protect • Leukocidins destroy neutrophils and macrophages • Hemolysisn break up red blood cells • Coagulase prevents or breaks up blood clots designed to localize infection • Ig. A proteases Destroy Ig. A antibodies

Bacteria moving into tissues • Kinases- destroy blood clots • Hyaluronidase works on mucopolysaccharide that holds cells together • Collagenase hydrolyses connective tissue collagen • Invasins destroy cytoskeleton of individual cells.

How bacterial pathogens damage the host cells. • Only some of the cell damage is caused by bacteria themselves – Some bacteria enter the host cell and damage as they leave – Some bacteria harm the cell as they enter

Penetration into the Host Cell Figure 15. 2

Bacteria Toxins • Cause the most damage • Toxins: poisonous substances produced by microbes • Toxigenicity: capacity of a microbe to produce toxin • Toxemia: presence of toxins in the blood • Toxoid: Inactivated toxin used in a vaccine • Antitoxin: Antibodies against a specific toxin

Exotoxins: • Produced by bacteria and released into surrounding area. Causes Disease – Cytotoxin or diphtheria toxin inhibits protein synthesis – Tetanus toxin prevents nerve transmission – Enterotoxins promote electrolyte and fluid loss from cells. – Neurotoxins (Botulinum toxin) prevent nerve transmission – Antibodies produced in response are antitoxins

Exotoxin Source Metabolic product Chemistry Fever? Neutralized by antitoxin LD 50 Mostly Gram + By-products of growing cell Protein No Yes Small

Exotoxins • A-B toxins or type III toxins Figure 15. 5

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

Endotoxins Figure 15. 6

Endotoxins • Are structures of the bacterium itself that cause the disease, like lipopolysaccharide (LPS) of gram negative bacteria – May be released when cells are killed by antibiotics – Cause fever and shock – May allow the bacteria to cross the blood brain barrier

A test for endotoxins. • Limulus amoebocyte lysate (LAL) used to detect endotoxins in drugs and on medical devices. – The amoebocyte will lyse in the presence of endotoxins causing a thickening of the media.

Endotoxins Source Metabolic product Chemistry Fever? Neutralized by antitoxin LD 50 Gram– Present in LPS of outer membrane Lipid Yes No Relatively large

Extra genetic material • Some bacteria may carry extra genes that help pathenogenisity – Plasmids (extra chromosomal) can carry genes for antibiotic resistance, toxins, capsules and fimbriae – Coagulase produced by Staphylococcus aureus – Fimbria in specific straines of E. coli

• Pathogenesis of nonbacterial microbes Viruses – Avoid immune system by growing inside host cell – May cause cell death or damage by growing and being released from the cell. – Casuse membranes to fuse • Fungi, Protozoa, Helminths and Algae – Symptoms caused by mixture of capsules, toxins, waste products and allergic response to the organism – Antigen switching allows to avoid hose immunity

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