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Evolving Pathogens:. Virulence. Jeremiah King & Jon Sheedy. Virulence. :the harm done by the pathogen to a host during the course of an infection. Picture courtesy www.cdc.gov/ncidod/ hip/flu_vac.htm. 3 models for explaining evolution of virulence.
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Evolving Pathogens: Virulence Jeremiah King & Jon Sheedy
Virulence :the harm done by the pathogen to a host during the course of an infection Picture courtesy www.cdc.gov/ncidod/ hip/flu_vac.htm
3 models for explaining evolution of virulence • Coincidental evolution hypothesis- virulence may not be direct product of selection but instead may be an accidental byproduct of selection of other traits. • Short-sighted evolution hypothesis- pathogens undergo many generations of evolution via natural selection in an individual host. The traits that enhance the current pathogen’s fitness may increase in fitness even if they are detrimental in other hosts upon transmission. • Trade-off hypothesis- pathogen populations would evolve toward lower virulence because the damage done to the hosts would be detrimental to the pathogens. • Bull 1994, Ewald 1994 and Levin 1999
Trade-off Hypothesis Pathogens cannot reproduce inside a host without doing the host some harm You would think pathogens with high within host reproductive rates should be transmitted to new hosts at high rates as well BUT… Reproducing at a high rate within a host will bring increased harm to the host. It is possible for pathogens to reproduce too fast THEREFORE… Natural Selection should favor pathogens that find an optimal balance between cost and benefits of harming the host
Messneger, Molineux and Bull (1999) • Tested trade-off hypothesis using E.coli and bacteriophage f1 • F1 has 2 modes of transmission • Vertically- between generations • Horizontally- from host to host through secreted virions • Picture courtesy www.harbinson.fslife.co.uk/ mutuality.htm
Messenger et al. isolated the two types of transmission in a culture of f1. • In other words, during vertical transmission they prevented the secreted virions from infecting other bacterial cells and during horizontal transmission the only way the phages were allowed to spread was through secretion • 2 sets of cultures for 24 days • Alternated 1 day long vertical transmission with brief horizontal transmission (24 horizontal transmission possibilities) • Alternated 8 day long vertical transmissions with brief horizontal transmission (6 horizontal possibilities) • @ end of study they measured phage virulence and phage reproductive rate
2 Predictions • There is a correlation between phage virulence and reproductive rate • Cultures subjected to 8 day long vertical transmission would evolve lower rates of reproduction and virulence than those subjected to 1 day long vertical transmission • .
Reasoning Reproduction in E.coli occurs slowly when phages are present approximately 1/3 the normal rate. Generation time for E.coli is 20 minutes therefore generation time with phages present is 60 minutes. Therefore if phages reproduce too quickly they will destroy the host. This will select for slower reproduction rates and virulence when transmission is vertical. On the other hand, when given more opportunities to transmit horizontally, the name of the game is numbers. The more numbers the phage can produce, the better the chance at survival. This will select for increased reproductive rates and virulence (Fig. 13.9)
Virulence in Human Pathogens • Ewald, Paul (1993,1994) considered the trade-off hypothesis in respect to human pathogens • Predictions: • Diseases transmitted by direct contact cannot afford to be virulent, while vectorborne disease can be highly virulent • Majority of directly transmitted diseases have mortality rates < 0.1%, while majority of vectorborne diseases have mortality rates > 0.1%. (Figure 13.10) • Diseases with a higher frequency of waterborne transmission would be more virulent • Most virulent of the nine bacteria studied was Vibrio Cholerae, which was responsible for the deadly cholera outbreak in London, 1854. (Figure 13.11)
Human Behavior Affecting the Severity of Human Diseases • Behavior selecting for increased virulence: • Dumping untreated sewage into rivers • Health care workers failing to thoroughly wash their hands • Behavior selecting for decreased virulence: • Keeping water supplies pure • Practicing good Hygiene
Take Home Message • Human pathogens or bacteriophages cannot afford to be highly virulent if they are transmitted by direct contact or through vertical transmission because they would most likely make the host too ill to further transmit the disease. Therefore a tradeoff must be made in order to acquire an appropriate balance between reproductive rate and virulence. • Human pathogens that are transmitted by vectors, such as mosquitoes, can afford to be highly virulent because the host does not need to be mobile. • Contaminated water plays the same role as an insect vector. It allows the pathogen to be highly virulent.