Host-Microbe Relationship Flashcards
How are we composed of microbes?
- our own bodies are only 1/2 our own (recent study found that we have resident bacterial community w/ an approximately equal number of cells to our own)
- our genomes contain a stunning number of ancient, endogenous, retroviruses (estimated to account for 5-8% of our genetic material!)
What important functions do microbes perform?
- lack to nitrogen fixing bacteria (decreased plant growth)
- w/o oxygenic microorganisms (increased atmospheric CO2)
- no microbes to break down waste (accumulating ‘waste’ biomass)
- some microbes are delicious
What are Koch’s postulates?
- microoganism must be found in abundance in all organisms suffering from disease, but should not be found in healthy organisms
- microorganisms must be isolated from a diseased organism & grown in pure culture
- cultured microorganism should cause disease when introduced into a healthy organism
- microorganism must be reisolated from the inoculated, diseased experimental host & identified as being identical to the original specific causative agent
How are Koch’s postulates related to real pathogens?
- strictly speaking, very few organisms act as “pathogens” as defined by Koch’s postulates (most are between obligate pathogens and non-pathogenic colonizers; ex: e-coli 0157 is a potentially serious human pathogen, but bovine commensal)
- there are very few strict pathogens (rabies - although maybe not in bats?; Yersinia pestis (plague) in people & domestic animals)
What is a pathogen?
organism capable of causing disease
virulence
relative ability of an organism to cause disease
virulence factor
property of an organism which allows it to establish w/in a host and/or cause disease
what is pathogenesis?
processes & host-organism interactions which lead to disease
What is the spectrum of host-microbe interactions from the host’s perspective?
- benefit (colonization w/ normal microbiota)
- indifference (latency)
- damage (disease)
When does disease happen?
- infections occur when (there is an overwhelming pathogen load and/or compromised host defenses)
- disease/pathology/damage results from (production of toxins and/or the invasion of tissues)
What are the fundamentals of pathogenesis?
- associate (enter body or reach site of infection: anatomical location, cell type, or receptor)
- multiply & evade (acquire & utilize nutrients, multiply & reach critical number while avoiding/countering host defenses)
- damage/co-opt (damage from pathogen, or host response +/- hijacking host processes. toxins, using host machinery for invasion, etc.)
- transmit (get out, survive, infect, repeat! efficiently shed infectious organism)
NOT A LINEAR PROCESS!
What are the overarching types of virulence factors?
- essential virulence genes (those which cause demonstrable damage to host)
- virulence associated genes (required for expression, secretion, or processing VF)
- virulence lifestyle genes (allow organism to colonize host or reach site of infection)
List of virulence factors:
- structures used for attachment
- flagella
- siderophores
- capsule
- secretion systems
- toxins
- superantigens
- enzymes
What are examples of structures used for attachment?
- Staphs & Streps - Microbial Surface Components Recognizing Adhesive Matrix Molecules (MSCRAMMs): proteins which bind to host ligands (fibrinogen, collagen, fibronectin, etc.); MSCRAMMs may also be anti-phagocytic by preventing opsonization)
- fimbriae: F4 fimbriae in E. coli - bind to intestinal epithelium in piglets up to ~8wk old; F5 fimbriae in E. coli - bind to epithelium in distal sm intestine in calves ~ first few days old
What are flagella used for?
reaching the site of infection
- motile E. coli swimming up ureters to cause ascending pyelonephritis following a lower UTI
- Brachyspira spp. moving through colonic mucous to reach intestinal crypt
what are siderophores?
- free iron is a limiting nutrient even in blood - its VERY tightly bound!
- these chelators allow bacteria to capture iron in a very low concentrated environment (Enterobactin, Yersiniabactin, Pyoverdin, Pyocyanin)
What is a capsule?
- polysaccharide struct
- interferes w/ innate immune system (prevents phagocytosis & attachment of complement)
- can also protect from bacteriophages!
What are the secretion systems?
- structures which transport molecules across the cell envelope
- type 3 secretion system of Salmonells is used to inject effector molecules into the host cells (needle like apparatus)
What are bacterial toxins?
wide variety of actions on target receptors / cells / tissues : endotoxin - lipopolysaccharide (LPS); exotoxin - (ex: botulinum toxin, shiga toxin, cholera toxin)
What are superantigens?
antigens which are able to non-specifically bind to & activate T-cell receptor, resulting in “cytokine storm”
What are the degrees of pathogenicity and what affects them?
- pathogenicity is non-binary
- can be accidental pathogen, opportunist facultative, or obligate pathogen
- is the organism pathogenic? is the host susceptible to infection? is the environment permissive to infection?
What is the damage-response framework?
What are some examples of saprophytes or environmental pathogens?
- Rhodococcus equi: cause of pneumonia in foals; otherwise healthy animals ~12 wks old; probably due to decline in maternal immunity; also seen in transplant, cancer, & AIDS patients
- Aspergillus: ubiquitous in nature; decomposing matter; cause of pneumonia & air sacculitis in birds; allergic airway disease in horses)
What are opportunistic pathogens?
- most clinically relevant organisms are probably best described as somewhere in the opportunistic spectrum
- gaining access to normally sterile site = infection (Staphylococcus spp.: mastitis, UTI, surgical site infections; Dermatophilus congolensis: cause of rain scald - occurs when wet, macerated skin is traumatized; E. coli: bacteremia/sepsis in most spp, UTI)
Difference btwn primary and secondary infections?
- is your patient’s infection secondary to a larger problem?
- determine WHY your patient has an infection, & then dealing with the underlying problem is critical!
- ex: is the disease in a dog (UTI) resulting from another disease? (UTI in dog secondary to diabetes, ectopic ureters, bladder cancer?)
- is the disease resulting from poor management? (failure to clean milking equipment leading to mastitis; overcrowding of pigs & failure to dock tails leading to tail biting & ascending infections of the spinal cord)
What are the three components of the epidemiological triad?
- favourable environment
- virulent agent
- susceptible host
What influences a favourable environment?
- agent & host are in same environment
- favourable conditions (ex: flooding vs drought)
- presence of vectors/reservoirs
- change that facilitates spread
- change that alters host susceptibility
What influences a virulent agent?
- possession of requisite virulence factors
- sufficient numbers
- change in virulence?
What influences a susceptible host?
- herd immunity
- individual susceptibility
- nutrition
- co-morbidities
- age
What is an example of the epidemiological triad at work?
Earthquake in Haiti
- host: > 1 million displaced people; cholera-negative, naiive population
- agent: vibrio cholerae - waterborne disease; tragically brought to Haiti by aid workers
- environment: devasted infrastructure in already desperately poor country; lack of adequate water sanitary systems (both sewage & drinking water)
What is a zoonoses?
- infectious disease caused by pathogen that has jumped from a non-human animal to a human
- typically, 1st infected human transmits infectious agent to @ least 1 other human, who, in turn, infects others
- in contrast, transmission can also occur via intermediate sp (vector), which carry disease pathogen w/o getting sick
- when humans infect other animals, it’s called reverse zoonosis
What should we think about in terms of interspecies transmission?
- why privilege discussions of interspecies transmission to a human perspective? (zoonoses, reverse zoonoses)
- what about transmission btwn different animals?
- think of transmission from the organism’s perspective
- tendency to classify as “zoonotic” or not is too reductive
BIG PIC: What are Koch’s postulates? Describe a situation where the postulates fall short?
- microoganism must be found in abundance in all organisms suffering from disease, but should not be found in healthy organisms
- microorganisms must be isolated from a diseased organism & grown in pure culture
- cultured microorganism should cause disease when introduced into a healthy organism
- microorganism must be reisolated from the inoculated, diseased experimental host & identified as being identical to the original specific causative agent
- strictly speaking, very few organisms act as “pathogens” as defined by Koch’s postulates (most are between obligate pathogens and non-pathogenic colonizers; ex: e-coli 0157 is a potentially serious human pathogen, but bovine commensal)
- there are very few strict pathogens
BIG PIC: What are 3 components of the epidemiological triad?
- susceptible host
- virulent agent
- favourable environment
