Microbial Pathogenesis - Lecture Notes | BIOL 2051, Study notes of Biology

Download Microbial Pathogenesis - Lecture Notes | BIOL 2051 and more Study notes Biology in PDF only on Docsity! Chapter 25 Microbial Pathogenesis Host-Pathogen Interactions • Infection = entry of pathogen or parasite • Infection doesn’t always cause disease • Most infections removed by immune system • Primary pathogens • Have ability to penetrate host defenses • Opportunistic pathogens • Cause disease only in compromised hosts • Immune system is defective • Break in tissue allows organism access to new site • Loss of other microflora (that defend) allows organism to bloom • Pathogenicity of organism • Measure of ability to cause disease • Determined by genetic makeup of organism • Infectious dose=ID50 • Number of organisms to colonize 50% of hosts • Virulence • Rate of lethal infections • Lethal dose=LD50 • Number of organisms to kill 50% of hosts Infection Cycle • Spread by direct contact (shaking hands) • Spread by indirect contact (breathing in bad air) • Contact with fomites  Inanimate object or substance that can carry infectious microbes • Horizontal transmission via vectors • Mosquitoes—yellow fever, malaria • Reservoir for disease organism (ex. bird that is bitten by infected mosquito) • May not show disease symptoms • Mode of entry depends on pathogen • Mucosal surfaces, wounds, insect bites Virulence Factors • Virulence genes • Encode factors allowing pathogen to invade host • Toxins, attachment proteins, capsules • Pathogenicity islands • Section of genome • Contain multiple virulence genes • Often encode related functions • Transferred as a block from other organisms very easily Virulence Factor  Structures & characteristics of pathogens that allow them to cause disease  Adhesion- ability to adhere to mucus membranes Virulence factors affecting adhesion: • Produced by Clostridium tetani which infects deep wounds Botulinum toxin • Prevents muscle contraction-results in respiratory or cardiac failure • Produced by Clostridium botulinum • Organism grows in improperly stored foods, where it produces toxin • Botulism is caused by ingesting toxin, not by infection with C. botulinum-honey can cause this in infants See Fig 26.18 Enterotoxins • Proteins that act on small intestine, cause diarrhea • Produced by food poisoning oranisms such as Clostridium, E. coli, Salmonella Examples of Entertoxins: • Cholera toxin • Produced by Vibrio cholera • Causes secretion of massive amount of water into small intestine (diarrhea)-death by dehydration Endotoxins • When Gram negative bacteria lyse, lipid A portion of LPS (Lipopolysaccharide) is released • LPS from many organisms, such as E. coli, Salmonella, Shigella, is toxic • Cause diarrhea, fever, vomiting-rarely fatal (only one that causes fever) Toxins Subvert Host Function • AB Toxins • B subunit binds to host cell • Delivers A subunit to cell • Often 5 B subunits form a pore for A entry • A subunit has toxic activity • ADP-Ribosyltransferase • Diphtheria toxin • Cholera toxin • ADP-Ribosylating Toxins • Cholera toxin • Ribosylates to overactivate adenylate cyclase • cAMP activates ion transport, water follows • Uncontrollable diarrhea • Diphtheria toxin • Ribosylates elongation factor 2 • Blocks ribosome function, cell dies • Forms pseudomembrane over trachea Surviving within the Host Once inside host cell, how to avoid death? • Cell ingests pathogens in phagosome • Some pathogens use hemolysin to break out • Shigella dysenteriae, Listeria monocytogenes • Phagosome fuses with acidic lysosome • Some pathogens secrete proteins to prevent fusion • Salmonella, Chlamydia • Some pathogens mature in acidic environment • Coxiella burnetii—Q fever Viral Pathogenesis Influenza • Influenza virus antigenic drift • Over long period of time • RNA Polymerase does not correct replication errors • Frequent mutations in hemagglutinin gene • If mutation allows virus to avoid immune system, virus spreads • New flu vaccine needed every year • Influenza antigenic shift • Two strains infect host at same time • Chicken or swine • Recombined viruses have mix of chromosomes • Immediate alteration of several genes • Cause of 1918 influenza outbreak • Largest single-year loss of life in recorded history HIV • HIV—Avoids host immunity by infecting immune cells • Binds multiple receptors for entry • CD4, chemokine receptor CCR-5 • Receptors on T cells • Infected cells secrete viral protein • Misregulates other immune system cells