Question

Medical Microbiology Tutorial: Evolution of Pathogen Virulence

Answer 1

\({\bf{Definition:}}\) (medical) the ability of an infectious agent to cause disease; the severity of the disease caused

\({\bf{Factors~That~Affect~Virulence:}}\)
- # of pathogens
- where the pathogens are located in the host
- how the host responds
- virulence factors (major focus of the tutorial): genes/proteins that enhance virulence (more specifically, the ability to invade the host, evade host defenses, and cause disease)

\({\bf{Examples~of~Virulence~Factors:}}\)
- adhesins (cell sufaces/surface components that increase adhesion to a host)
- secretion systems (protein complexes for secretion of substances that increase virulence)
- toxins (harmful substances that target other cells)
and others

Answer 2

\({\bf{Hypotheses~of~Virulence:}}\)

conventional wisdom: in pathogens, there is a tendency to select against harming the host and towards a commensalism model

trade-off: there is a trade-off between transmission and virulence

multi-infection: the interactions between multiple clones within a host can increase or decrease virulence

**** happens hypothesis: transmission and non-transmission elements are de-coupled

Answer 3

\({\bf{Conventional~Wisdom:}}\)
- basic model:

(transmission between susceptible and infecteds) - (mortal virulence among the infected)

so the fitness of the pathogen is expected to be maximized when the mortal virulence approaches 0 (drive towards commensalism)

- assumes transmission and virulence are independent
- doesn't explain why some diseases have been increasing in virulence

Answer 4

\({\bf{Trade-Off~Hypothesis:}}\)
- transmission and virulence are positively associated
- high mortal virulence does not necessarily prohibit transmission (the pathogen can be transmitted regardless if the host is alive or not)
- "optimal" level of virulence is selected for

Answer 5

\({\bf{Multiple-Infection~Hypothesis:}}\)
- conventional wisdom assumes monoclonal pathogens and epi selection only between hosts
- multiple infection hypothesis accounts for multiple clones and selection within a host, between strains
- traits that increase reproduction and transmission are selected for within a host
- selection occurs faster for pathogens due to much higher populations and faster gen times
- individual control of growth --> leads to higher virulence in mixed pathogen populations
- collective control of growth --> lower virulence in mixed pathogens (competition between pathogens)

Answer 6

\({\bf{Coincidental~Evolution~Hypothesis:}}\) (**** happens)
- separation of transmission and virulent components
ex: Pneomococcus:
> in the nose: transmission, asymptomatic
> in the blood: virulence, symptomatic

selection for virulence traits can happen outside of the place where the actual virulence occurs

ex: C. tetani: the outside environment selects for the production of toxins. this VF increases virulence in the host.

Answer 7

\({\bf{Synergistic~Interactions:}}\)

- different species can act synergistically (one species can enhance virulence in another)
ex: P. aeruginosa and S. aureus, when present together in an in vitro wound model, increase each other's virulence

- S. auerus increases the formation of biofilms --> increases growth of P. aeruginosa, which enhances the degradation of antibiotics, increasing S. aureus growth

Answer 8

\({\bf{Sources:}}\)
- lecture notes

https://www.ncbi.nlm.nih.gov/pubmed/25156721
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1693375/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC520815/
https://www.medicinenet.com/script/main/art.asp?articlekey=6911
https://www.ncbi.nlm.nih.gov/books/NBK8526/

Answer 9

Bonus set of flashcards:

https://quizlet.com/454696771/med-micro-evolution-of-pathogenesis-flash-cards/