Quiz 2 - Mulvey - Pathogenesis Flashcards
What are opportunists/pathobionts?
Under normal circumstance, organism does not cause disease, but can be pathogenic under some conditions
*Immunocompromised
Human microbiota - most bacteria (by number) where in the body?
Colon
*Stomach is least moving down thru colon there is an increase
What else increases?
Diversity
What does the microbiota do?
Help with digestion
Help protect against infiltration of pathogenic bacteria by taking up space and outgrowing pathobionts (C. diff)
What is colonization resistance?
Microbiota inhibits colonization by newcomers
Clostridium difficile is what?
Gram (+) obligate anaerobe
What allows c diff to proliferate?
Broad spec antibiotic treatment that alters healthy gut microbiota
How does c diff survive antibiotics?
Resistance genes and mutations
Biofilm formation
Spore formation
What will c diff sporulate?
Shortage of nutrients
*Antibiotic treatments can stimulate spore formation, creating a super shedding state that promotes dissemination of the pathogen
Clostridium spores have a protective coat consisting of what 5 things?
Cell membrane
Thick peptidoglycan mesh
Another cell membrane
Wall of keratin-like protein
Outer layer of exosporium
How to kill spores?
Autoclaves
*Makes equipment sterile
**Most antibiotics, hand sanitizers won’t kill spores
What two genera form spores?
Clostridium
Bacillus
C diff causes what terrible things?
Nosocomial infections
Tetanus (C tetani)(soiled IV)
Gas gangrene
Food bourne Infections (botulism, c perfringens)
Bacillus forms what?
Anthrax (Soiled IV)
B cereus - food bourne infections
What are 5 factors that facilitate bacterial infection and survival w/in a host?
Ability to outcompete commensalism at many stages
Attachment to host cells and tissue via ADHESINS
Evasion of innate and adaptive responses
Acquisition of limiting nutrients - Iron, amino acids
Dissemination w/in a host and transmission to new hosts - Ability to break down or cross tissue barriers
Walk me thru a microbe being phagocytozed?
Microbe bound by phagocyte
Phagocyte membrane zips up around microbe and ingests it
That endocytosis leads to lysosome at the phagolysosome
The microbe is killed in the lysosome via proteases and drop in pH
How do some bacteria evade host defenses?
Possess virulence factors that prevent uptake and destruction by phagocytes
Possess factors that promote survival in inhospitable places in the body
Facultative intracellular bacteria regulate their genes to know if they are inside or outside a host cell
What are some survival strategies w/in extracellular environments?
Capsules
-Prevent complement deposition or mask C3b from interaction with phagocytes
Vary surface exposed antigens that allow outgrowth of antigenically novel clones. (Ability to change antigenicity (what it looks like to the host cells) to evade the host via point mutations, etc)(Phase shifting - on/off phase)
Secretion of molecules that interfere with host defenses
- Toxins
- Enzymes
Some bacteria have mastered survival w/in hosts. Name 4 ways how.
Resistant to reactive oxygen species and nitric oxide
Neutralize phagolysosome contents
Prevention of phagolysosome fusion
-Legionella, mycobacterium
Escape from the phagosome
-LIsteria, francisella, rickettsia
Tell me about listeria monocytogenes.
Gram (+) facultative anaerobe
Causes listeriosis 3rd leading cause of death to foodbourne pathogens
Lettuce or cantaloupes
Listeria internalins ________ surface receptors and trigger a cascade. These result in ___________ of the bacteria by host cells that are not considered professional _________.
Engage
Internalization
Phagocytes
Tell me how listeria uses motility intracellularly.
FINISH THIS
What are toxins?
Virulence factors (excreted or not) that are toxic to human or animal or plant cells
Toxins affect host activities. Name some.
Aberrant activation of host inflammatory responses (LPS)
Act at host surface or w/in cells to inhibit or activate signaling cascades, alter membrane and protein trafficking
-BoTox
Disruption of host cell membranes, trigger ion fluxes, and alter signaling pathways
What is endotoxin?
LPS
*Lipid A moiety of LPS
**Body triggers an inflammatory response
What are exotoxins?
Proteins that are released by bacteria that can cause disease manifestations
What are enterotoxins?
Act in GI tract to cause infectious diarrhea (Cholera toxin), or food poisoning (Bacillus cereus)
What are neurotoxins?
Act on nerves/synapses to cause paralysis
What are pyrogenic exotoxins?
Stimulate release of cytokines that can cause rash, fever, and toxic shock syndrome
What are tissue invasive exotoxins?
Allow bacteria to penetrate or circumvent cell and tissue barriers (DNAses)
Other exotoxins - functions?
Many out there. Can affect very specific host factors, though function is not always clear (Anthrax)
What are superantigens?
Bind class II MHC - recognized by less variant regions of TCR families
*Forms bridge b/t APC and T cells and results in massive outpouring of cytokines - T cells become activated and then exhausted and die
**Can cause diarrhea
What is quorum sensing?
Allows bacteria to communicate and act in groups (Like in biofilm)
Many protein toxins, especially those that act intracellularly consist of 2 parts, the A and B subunits. What are A/B toxins?
A subunit - Responsible for the enzymatic activity of the toxin
B subunit - Mediates binding to a specific receptor and transfer of the A subunit across the membrane
What are some toxins that are A/B toxins?
Diphtheria - ADP ribosylates EF-2 - Inhibition of protein biosynthesis
Shiga - Cleavage of ribosomal RNA - Inhibition of protein biosynthesis
Pertussis - ADP ribosylates G protein - Reduced phagocytosis activity
Cholera - ADP ribosylates G protein - Increased chloride secretion
Botulinum - Cleavage of synaptobrevin - Flaccid paralysis
Tetanus - Cleavage of synaptobrevin - Spastic paralysis
How do A/B toxins enter host cells?
Fusion w/ endosomes, and release of A subunits triggered by low pH
*Via retrograde transport
What is a toxoid?
Chemically modified toxin from a pathogenic microorganism, which in no longer toxic, but still antigenic and can be used as a vaccine.
Botox?
- Produced by blostridium botulinum
- Absorbed from stomach after ingestion of contaminated food
- Inhibits presynaptic release of excitatory NT (Ach) from peripheral nn at neuromuscular junctions
- Causes flaccid paralysis and respiratory paralysis
Tetanus?
- Produced by clostridium tetani
- Associated with deep wound infections, and it is also a leading cause of infant death worldwide
- Blocks release of inhibitory NTs (glycine and GABA [gamma-aminobutyric acid])
- Results in imbalance of excitatory and inhibitory effects of motor neurons
- Leading to rigid mm contractions and spastic paralysis of respiratory mm
