Transcript E3_Virulence_2011Part 1 - MicrobialEvolution.org

The Evolution of Virulence
E3: Lecture 14
What is Virulence?
• Most generally, virulence is defined as a
pathogen’s ability to do damage to its host.
• Such damage might entail:
- Increased rate of host death
- Decreased rate of host growth
bird flu
anther smut
- Decreased rate of host reproduction
• Pathogens can differ dramatically in their
virulence; some are extremely harmful
(e.g., Ebola), while some do not damage
their host severely (e.g., Herpes Simplex).
• What are the factors that contribute to
increases or decreases in the virulence of a
pathogen?
• Can a highly virulent pathogen become a
beneficial symbiont?
Ebola Virus
Herpes Virus
Rickettsia prowazekii
mitochondria
Virulence can Change
• In 1966, a microbiologist,
Kwang Jeon, was studying
amoebae when his cultures
became infected with
bacteria.
• Most of the amoebae were
killed by the bacterial
disease, but a few survived.
• After many generations, the
amoebae again appeared
healthy, but these protists still
housed many bacterium.
Kwang Jeon
an amoeba with x-bacteria
most amoebae die from
bacterial infection
antibiotic applied
• Jeon applied an antibiotic
that killed the bacterium.
• Interestingly, without the
bacterial endosymbiont, the
amoeba host now died!
evolutionary change
virulent pathogen
essential symbiont
The Evolution of Virulence
Lecture Outline
• Introduction to virulence theory
• Transmission mode experiment
• Transmission timing experiment
• Metapopulation experiment
• Summary
The Evolution of Virulence
Lecture Outline
• Introduction to virulence theory
• Transmission mode experiment
• Transmission timing experiment
• Metapopulation experiment
• Summary
Conventional Wisdom and Tradeoff Theory
• The conventional wisdom is that
pathogens should lower their virulence:
- A healthy long-lived host provides future
opportunities for spread.
hantavirus
• Under this conventional view, pathogens
virulent to their hosts are imports from
other host species where the relationship
is more benign– evolutionary change
should favor lower virulence.
P
- Within-host competitive ability
P
Host
P P P P P
P
Host
P P P
Host
Host
P P P
P
Host
P
Host
P
P
P
virulence
P P
• Potential tradeoffs with virulence:
- Transmission potential
P
P
comp. ability
• However, this conventional wisdom
treats virulence as an independent trait.
There may be cases where virulence and
other pathogen traits covary.
deer mouse
transmission
- A reproducing host provides future homes
for a pathogen’s offspring.
P
P
virulence
Factors Affecting Virulence
Take 3 minutes to talk
to your neighbor about
the following:
What factors do you think will
affect the success of P
versus P ? Think of
environmental factors,
conditions in the host
population, life history of the
pathogen, etc…
Competitive-virulence tradeoff
Transmission-virulence tradeoff
P
P
P
P
P P
P P P
Host
Host
P P P
Host
P
P P P P P
P
P
Host
P
P
Host
P
P
Host
P
P
P
• Some important factors include:
- Host density
- Host resistance
- Mode of transmission
- Timing of transmission
myxoma - rabbit
l phage - E.coli
anthrax spores
cholera - copepod
- Frequency of superinfection
- Viability of the pathogen outside host
- Environmental disease reservoirs
The Evolution of Virulence
Lecture Outline
• Introduction to virulence theory
• Transmission mode experiment
• Transmission timing experiment
• Metapopulation experiment
• Summary
Partner Fidelity and Virulence
• The mode of transmission is expected to influence
the level of virulence in a host-pathogen relationship:
-Vertical: Parents pass on pathogens to their offspring.
VERTICAL TRANSMISSION
host
pathogen
P
H
t0
-Horizontal: Pathogens move between unrelated hosts.
• With high partner fidelity (e.g., with vertical
t1
PH
PH
transmission), investments made by one partner can
pay off in the future with the same partner (or
destructive behavior feeds back negatively for both HORIZONTAL TRANSMISSION
partners).
t
P
• With low partner fidelity (e.g., with horizontal
transmission), taking advantage of one’s partner can
pay off as long as there is another new partner
around the corner to exploit.
H
H
P
H
P
H
0
H
t1
• The density of hosts may influence the mode of
transmission (lowvertical and highhorizontal)
• Think about how you invest in your own car versus
a rental car (e.g., how thoroughly do you clean it,
what grade of gas do you put in the tank, etc.)
high partner fidelity
low partner fidelity
Experimental System to Explore Virulence
• The filamentous phage are virus that infect a
bacterium through its pilus (a bacterial STD)
• Some properties of filamentous phage:
- Do not kill their host, but are excreted continuously
through the bacterial membrane
pathogen:
filamentous phage
- Infected bacteria are resistant to further phage attack
- Infected bacteria divide at a slower rate than noninfected cells
- Infected bacteria pass on the virus to daughter cells
- There are not strict packaging requirements on the
phage DNA, so extra genes can be incorporated into the
phage genome
host: E. coli
• This is a nice system to explore the evolution of
virulence because the mode of transmission can be
experimentally controlled.
host pilus