Evolving Pathogens:
Jeremiah King & Jon Sheedy
: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
1. Alternated 1 day long vertical transmission with brief
horizontal transmission (24 horizontal transmission
possibilities)
2. 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
1. There is a correlation between phage virulence and reproductive
rate
2. 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:
1. 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)
2. 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
1. 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.
2. 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.
3. Contaminated water plays the same role as an insect vector. It
allows the pathogen to be highly virulent.