Lecture 7 symbiosis to disease 2011

Lecture 7 symbiosis to disease 2011 -...

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Symbiosis to disease- Important  Pathogens
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Evolution Why is it advantageous for a microbe to  harm or kill its host?
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Symbiosis to disease Why would it be advantageous for a soil  microbe, that rarely comes in contact  with a human, to retain virulence  factors? Why are only some strains of a species  pathogenic? 
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Infection vs intoxication
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Common Steps in Infections 1. Encounter (contact) 2. Entry (portals) 3. Establish Infection (colonization) 4. Cause Damage (clinical manifestations)
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6 Virulence Pathogenicity of organism Measure of ability to cause disease Determined by genetic makeup of organism Infectious dose = ID 50 Number of organisms to colonize 50% of hosts Virulence Frequency of lethal infections Lethal dose = LD 50 Number of organisms to kill 50% of hosts
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7 Virulence Factors Virulence genes Encode factors allowing pathogen to invade host Toxins, attachment proteins, capsules Pathogenicity islands Contain multiple virulence genes Often encode related functions E.g., protein secretion system, toxin production Transferred as a block from other organisms Often flanked by phage or plasmid genes Often have GC content different from rest of genome
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8 Microbial Attachment Human body expels invaders Mucosa, dead skin constantly expelled Liquid expelled from bladder Coughing, cilia in lungs Expulsion of intestinal contents Bacteria must adhere to host tissue Pili (fimbriae) Hollow fibrils with tips to bind host cells Adhesins—surface proteins bind host cells
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9 Toxins Subvert Host Function Five categories of protein exotoxins Cause host cell membrane leakage Block protein synthesis Block 2nd messenger pathways Superantigens overactivate the immune system Proteases cleave host proteins
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10 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 Toxins Subvert Host Function Vibrio cholera e
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11 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 ADP-Ribosylating Toxins orynebacterium diphtheriae
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12 Anthrax toxin—two active toxins Edema factor raises cAMP levels  Causes fluid secretion, tissue swelling Lethal factor cleaves protein kinases Blocks immune system from attacking Gram-negative lipopolysaccharide Component of outer membrane Endotoxin in lipid A component Activates inflammatory response Can cause toxic shock Toxins Subvert Host Function Bacillus anthracis
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Lecture 7 symbiosis to disease 2011 -...

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