Chapt 25 Lecture- Microbial Pathogenisis

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traylsu  on May 9, 2011

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Chapt 25 Lecture- Microbial Pathogenisis

Infection
entry of pathogen or parasite
(doesnt always cause disease- most infections are removed by immune system)
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Definitions

Infection entry of pathogen or parasite
(doesnt always cause disease- most infections are removed by immune system)
Primary pathogens have ability to penetrate host defenses
Opportunistic pathogens cause disease only in compromised host
(weakened immune system)
(break in tissue allows organisms access to new site)
(loss of other microflora allows organisms 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
Lethal dose = LD50 number of organisms to kill 50% of hosts
Infection cycle spread by:
direct contact - body fluids
indirect contact
Spread by indirect contact contact with fomite - inanimate objects or substances that can carry infectious microbes (eg. door knobs)
Spread by indirect contact Horizontal transmission via vectors
eg. mosquitos - yellow fever, malaria, West Nile virus
mosquito may not show symptoms of those diseases however
Mode of entry of pathogen mucosal surface, wounds, insect bites
VIRULENCE FACTORS: virulence genes Virulence genes encode factors that allow pathogen to iINVADE host
Examples of virulence factors toxins
attachment proteins
capsules
Pathogenicity islands section of genome - contains multiple virulence genes that code for related function
How are pathogenicity islands transferred? As a block from one organism to another
Virulence Factor definition structure and characteristics of pathogens that allow them to cause disease
Adhesion ability to adhere to mucus membranes
Virulence Factors affecting ADHESION capsule
fimbriae/pili
adhesins
Capsule outer polysach layer- helps attachment- protects from phagocytosis
fimbriae/pili necessary for some orgs to attach.. Neiserria and E. coli
Adhesins surface proteins that bind host cells eg. S. pyogenes
Invasion pathogens must be able to penetrate epithelium of skin
they reach inner layer of skin cells through lesions or mucus membrane
Colonization Once it has invaded the host, it can establish itself and grow
Virulence Factors affecting INVASION & GROWTH O & Vi} salmonella
Siderophores
Leukosidin
O antigen - salmonella O - (somatic antigen- part of LPS) cell surface polysaccharide- prevents phagocytosis
Vi antigen- salmonella Vi - (capsular antigen) prevents complement binding & antibody mediated killing
Siderophores compound that binds iron & make it available to the bacterial cell
Leukosidin Staph aureus produces Leukosidin
Leukosidin lyses white blood cells, decreasing host resistance
Localized infection organisms grow locally at site of invasion
Systemic infection organisms spread through body using blood or lymphatic systems
How do pathogens spread (disseminate) in the body? they make virulence factors - many of these are enzyme which break down tissue
Examples of virulence factors that break down tissue Hyaluronidase
Collagenase
Streptokinase
Hemolysins
Hyaluronidase destroys polysaccharides that glue animal cells together
Collagenase breaks down collagen - produced by clostridium
Streptokinase breaks down fibrin clots made by host to prevent spread - made by Strep pyogenes
Hemolysins disrupt cytoplasmic membrane of animal cells - lyse red blood cells
3 MAJOR GROUPS OF TOXINS Exotoxins (worst)
Enterotoxins
Endotoxins
EXOTOXINS protein secreted by bacteria that can damage tissues far away from infection site
Examples of EXOTOXINS Diphtheria toxin
Tetanus toxin
Botulinum toxin
Diphtheria toxin inhibits protein synthesis
When Corynebacterium diphtheriae is lysogenized by phase β, tox genes are formed that makes the toxin
Tetanus toxin Acts on motor neurons- causes continual contraction of muscles (lead to lock jaw)
produced by Clostridium tetani- infects deep wounds
Botulinum toxin prevents muscle contraction - results in respiratory /cardiac failure
produced by Clostridium botulinum
Botulism caused by ingesting toxin from canned foods
ENTEROTOXINS proteins that act on small intestine (cause diarrhea)
produced by food poisoning organisms eg. Clostridium, E coli, Salmonella
Example of ENTEROTOXIN cholera toxin
produced by vibriocholera
How does cholera toxin work? Causes secretion of massive amounts of water in small intestine (diarrhea) - death by dehydration
ENDOTOXINS when gram negative bacteria lyse
lipid A portion of LPS is released
Organisms that release toxic Lipid A from LPS E coli
Salmonella
Shigella
causes diarrhea, fever, vomiting
Toxins that ****s up host function AB toxins
ADP Ribosylating toxins
AB toxins B subunit binds to host cell
delivers A subunit to cell
5 B subunits form pore for lipid A entry

'A' subunit is toxic- releases ADP Ribosyltransferase
ADP Ribosylating toxins Cholera toxins
Diphtheria toxins
Cholera toxins ribosylates to overactivate adenylate cyclase
cAMP activates ion transport, water follows} uncontrollable diarrhea
Diphtheria toxins ribosylates elongation factor 2 <-- cell that makes proteins
Diphtheria toxin blocks ribosome function - cell dies
Diphtheria toxin forms pseudomembrane over trachea
How do pathogens survive once they enter host cell cells ingest pathogens in phagosome - fuses with lysosome
but some pathogens secrete proteins to prevent fusion (Salmonella, Chlamydia)

some pathogens mature in acidic environment (Coxiella burnetti - Q fever)
How do pathogens survive once they enter host cell some pathogens use hemolysin to break out and leave (Shigella dysenteriae, Listeria monocytogenes)
VIRUSES influenza
HIV
Influenza virus antigenic DRIFT RNA polymerase does not correct replication errors - mutations in haemagglutinin gene
haemagglutinin gene forms spikes on influenza virus- helps them attach to host
Mutation in haemagglutinin gene allows virus to avoid immune system - virus spreads
new vaccine needed each year
Influenza virus antigenic SHIFT two strains infect host at the same time (chicken or swine)
recombined virus have mix of chromosomes (alters several genes)
cause of 1918/1919 influenza outbreak - largest loss of life in a single year
HIV avoids host immunity by infecting immune cells
binds multiple receptors for entry (CD4 & CCR-5-chemokine receptors)
Cells infected by HIV secrete viral protein, which misregulates other immune system cells

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