Microbial Pathogenesis (Ch. 25, Lec. 21)
Tuesday, December 1, 2020 11:30 AM
25.1: Host-Pathogen Interactions
• Pathogens: bacterial, viral and fungal parasitic agents of disease.
• Infection: a pathogen/parasite enters or beings to grow on a host; doesn’t always imply disease.
○ Some infections can be latent--the infectious organism cannot be found by culture.
• Primary pathogens: cause disease in healthy hosts. Ex. Ebola, HIV
• Opportunistic pathogens: cause disease only in compromised hosts, or following entry into unprotected sites(ie cut). Ex. Pneumocystis jirovecii,
life-threatening in AIDS patients.
• Pathogenicity: an organism's ability to cause disease. Defined in terms of infectivity, virulence, genetic makeup.
• Virulence: measure of the severity of the disease. Ex. Rhinoviruses not virulent.
○ Infectious dose(ID50): # of pathogens required to cause infection in 50% of hosts.
○ Lethal dose (LD50): # required to cause death in 50% of hosts.
• Infection cycle: route of transmission of an infectious organism. Direct or indirect.
○ Horizontal transmission: passage from one host to another w/in the same generation.
• Fomites: thru inanimate objects.
• Vehicles: ingested or inhaled materials.
○ Vertical transmission: passage from a mom to her fetus during pregnancy or birth.
• Vectors: intermediaries that transfer the virus from infected to uninfected individuals.
• Reservoirs: an animal, bird, or arthropod(insect) that normally harbors the pathogen often w/o exhibiting disease. Ex. Yellow fever. Mosquitoes can
pass the virus to future generations thru vertical transmission.
• Portals of entry: how an infectious agents enters the body. Ex. Parenteral route--direct injection into the bloodstream.
• Immunopathogenesis: when the immune response to a pathogen is contributing cause of pathology/disease. Often causes major tissue and organ
damage.
• Pathogen's growth + host's immune response will also affect host's normal microbiota.
○ Ex. Diarrhea reduces overall # of gut microbiota.
• Virulence factors: factors that promote disease of a pathogen (toxins, attachment proteins, capsules, other devices).
• To give way to pathogenicity, virulence genes must meet all of the molecular Koch's postulates:
1. The phenotype should be associated w/ pathogenic strains of a species.
2. Specific inactivation of the of the gene should lead to loss in virulence/pathogenicity. Gene should be isolated by molecular methods.
3. Reversion or replacement of the mutated gene(put gene back into organism) should restore pathogenicity.
• Some virulence genes reside on plasmids or in phage genomes.
• Pathogenicity islands: a cluster of virulence genes in bacterial pathogens; encode virulence factors.
○ Most islands appear to have been horizontally transmitted via conjugation or transduction: unique CG/AT ratio(compared to core genome),
linkage to a tRNA gene(insertion to a foreign gene), association w/ homology to phage/plasmid genes.
• Pathogens can evolve thru horizontal gene transfer.
○ Ex. Streptococcus pyogenes. Large-scale genome sequencing data -> epidemics are caused by clonal replacement events rather than re-
emergence of preexisting clones.
25.2: Microbial Attachment: 1st Contact
1. Adhesion: viruses attach to host cells thru their capsid/envelope proteins. Bacteria bind to specific host (amino terminus of fibronectin, attach to
pharyngeal epithelium) cell factors, ie attach via pili. -> Sore throat
a. Adhesin: any microbial factor that promotes attachment. (Protein F)
b. Pili (fimbriae): hair-like appendages. Type I (adheres to carbs on host membranes, static) and Type II (attaches via assembly and
disassembly/Twitch Motility).
c. Some bacteria possess adhesins that are not pili. Ex. M protein.
• Pathogens rely on very specific surface structures (receptors) to recognize and attach to appropriate host cells. -> A person can be less susceptible
to certain infections:
○ Person-to-person differences in receptor structures are possible.
○ Ex. HIV binds to C-C chemokine receptor type 5 (CCR5); individuals w/ CCR5 mutation are resistant to HIV infection.
• Biofilms: pop of bacteria attaching to surfaces.
○ Enable persistent adherence, resistance to host defenses, and tolerance to antimicrobial agents.
25.3: Toxins Subvert Host Functions
• Bacterial toxins can be divided into 2 main types:
1. Exotoxins: proteins(not stable in heat) produced/secreted by many bacterial types. Kill host cells and unlock their nutrients.
2. Endotoxins: Lipid A of the LPS in Gram-negative bacteria. Leads to hyperactive host immune system that causes harm.
• AB exotoxins: exotoxins w/ 2 subunits that work together to disrupt host cell functions.
• A subunit: toxicity-associated factor.
• B subunit: entry-associated factor; binds to host cell and delivers A subunit.
•
•
• Cholera toxin: a AB5 exotoxin made by Vibrio Cholerae. B binds to intestinal cell membranes and triggers endocytosis of cholera toxin complex. -> A
"ADP-ribosylates"(activates adenyl cyclase) host cell, which leads to INCed cAMP levels. -> cAMP activates ion transporters that cause water to
leave the cell. -> Diarrhea. DISRUPTS SIGNALING FUNCTIONS
○ Cholera is an easily treatable disease. Can be fixed through oral rehydration or intravenous administration of fluids. If left untreated, it can kill pt
following onset of symptoms.
○ A subunit is a toxic enzyme that can repeatedly turn a controlled signal molecule ON -> continuously pumps OUT salt of intestinal lining cells.
• Bacterial toxins are more deadly than chemical poisons:
○ Chemicals attack one-by-one -> many molecule of ie cyanide are needed to kill a cell.
○ One bacterial toxin is needed to perform the same js over and over again (reusable enzyme).
Tuesday, December 1, 2020 11:30 AM
25.1: Host-Pathogen Interactions
• Pathogens: bacterial, viral and fungal parasitic agents of disease.
• Infection: a pathogen/parasite enters or beings to grow on a host; doesn’t always imply disease.
○ Some infections can be latent--the infectious organism cannot be found by culture.
• Primary pathogens: cause disease in healthy hosts. Ex. Ebola, HIV
• Opportunistic pathogens: cause disease only in compromised hosts, or following entry into unprotected sites(ie cut). Ex. Pneumocystis jirovecii,
life-threatening in AIDS patients.
• Pathogenicity: an organism's ability to cause disease. Defined in terms of infectivity, virulence, genetic makeup.
• Virulence: measure of the severity of the disease. Ex. Rhinoviruses not virulent.
○ Infectious dose(ID50): # of pathogens required to cause infection in 50% of hosts.
○ Lethal dose (LD50): # required to cause death in 50% of hosts.
• Infection cycle: route of transmission of an infectious organism. Direct or indirect.
○ Horizontal transmission: passage from one host to another w/in the same generation.
• Fomites: thru inanimate objects.
• Vehicles: ingested or inhaled materials.
○ Vertical transmission: passage from a mom to her fetus during pregnancy or birth.
• Vectors: intermediaries that transfer the virus from infected to uninfected individuals.
• Reservoirs: an animal, bird, or arthropod(insect) that normally harbors the pathogen often w/o exhibiting disease. Ex. Yellow fever. Mosquitoes can
pass the virus to future generations thru vertical transmission.
• Portals of entry: how an infectious agents enters the body. Ex. Parenteral route--direct injection into the bloodstream.
• Immunopathogenesis: when the immune response to a pathogen is contributing cause of pathology/disease. Often causes major tissue and organ
damage.
• Pathogen's growth + host's immune response will also affect host's normal microbiota.
○ Ex. Diarrhea reduces overall # of gut microbiota.
• Virulence factors: factors that promote disease of a pathogen (toxins, attachment proteins, capsules, other devices).
• To give way to pathogenicity, virulence genes must meet all of the molecular Koch's postulates:
1. The phenotype should be associated w/ pathogenic strains of a species.
2. Specific inactivation of the of the gene should lead to loss in virulence/pathogenicity. Gene should be isolated by molecular methods.
3. Reversion or replacement of the mutated gene(put gene back into organism) should restore pathogenicity.
• Some virulence genes reside on plasmids or in phage genomes.
• Pathogenicity islands: a cluster of virulence genes in bacterial pathogens; encode virulence factors.
○ Most islands appear to have been horizontally transmitted via conjugation or transduction: unique CG/AT ratio(compared to core genome),
linkage to a tRNA gene(insertion to a foreign gene), association w/ homology to phage/plasmid genes.
• Pathogens can evolve thru horizontal gene transfer.
○ Ex. Streptococcus pyogenes. Large-scale genome sequencing data -> epidemics are caused by clonal replacement events rather than re-
emergence of preexisting clones.
25.2: Microbial Attachment: 1st Contact
1. Adhesion: viruses attach to host cells thru their capsid/envelope proteins. Bacteria bind to specific host (amino terminus of fibronectin, attach to
pharyngeal epithelium) cell factors, ie attach via pili. -> Sore throat
a. Adhesin: any microbial factor that promotes attachment. (Protein F)
b. Pili (fimbriae): hair-like appendages. Type I (adheres to carbs on host membranes, static) and Type II (attaches via assembly and
disassembly/Twitch Motility).
c. Some bacteria possess adhesins that are not pili. Ex. M protein.
• Pathogens rely on very specific surface structures (receptors) to recognize and attach to appropriate host cells. -> A person can be less susceptible
to certain infections:
○ Person-to-person differences in receptor structures are possible.
○ Ex. HIV binds to C-C chemokine receptor type 5 (CCR5); individuals w/ CCR5 mutation are resistant to HIV infection.
• Biofilms: pop of bacteria attaching to surfaces.
○ Enable persistent adherence, resistance to host defenses, and tolerance to antimicrobial agents.
25.3: Toxins Subvert Host Functions
• Bacterial toxins can be divided into 2 main types:
1. Exotoxins: proteins(not stable in heat) produced/secreted by many bacterial types. Kill host cells and unlock their nutrients.
2. Endotoxins: Lipid A of the LPS in Gram-negative bacteria. Leads to hyperactive host immune system that causes harm.
• AB exotoxins: exotoxins w/ 2 subunits that work together to disrupt host cell functions.
• A subunit: toxicity-associated factor.
• B subunit: entry-associated factor; binds to host cell and delivers A subunit.
•
•
• Cholera toxin: a AB5 exotoxin made by Vibrio Cholerae. B binds to intestinal cell membranes and triggers endocytosis of cholera toxin complex. -> A
"ADP-ribosylates"(activates adenyl cyclase) host cell, which leads to INCed cAMP levels. -> cAMP activates ion transporters that cause water to
leave the cell. -> Diarrhea. DISRUPTS SIGNALING FUNCTIONS
○ Cholera is an easily treatable disease. Can be fixed through oral rehydration or intravenous administration of fluids. If left untreated, it can kill pt
following onset of symptoms.
○ A subunit is a toxic enzyme that can repeatedly turn a controlled signal molecule ON -> continuously pumps OUT salt of intestinal lining cells.
• Bacterial toxins are more deadly than chemical poisons:
○ Chemicals attack one-by-one -> many molecule of ie cyanide are needed to kill a cell.
○ One bacterial toxin is needed to perform the same js over and over again (reusable enzyme).
