1. The Evolution of Virulence E3: Lecture 14

2. 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 - 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 VirusHerpes Virus bird fluanther smut Rickettsia prowazekiimitochondria

3. 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. Jeon applied an antibiotic that killed the bacterium. Interestingly, without the bacterial endosymbiont, the amoeba host now died! Kwang Jeonan amoeba with x-bacteria most amoebae die from bacterial infection many generations antibiotic applied amoebae died without the bacterial presence! virulent pathogenessential symbiont evolutionary change

4. The Evolution of Virulence Lecture Outline Introduction to virulence theory Transmission mode experiment Transmission timing experiment Metapopulation experiment Summary

5. The Evolution of Virulence Lecture Outline Introduction to virulence theory Transmission mode experiment Transmission timing experiment Metapopulation experiment Summary

6. Host 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. - A reproducing host provides future homes for a pathogen’s offspring. 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. However, this conventional wisdom treats virulence as an independent trait. There may be cases where virulence and other pathogen traits covary. Potential tradeoffs with virulence: - Transmission potential - Within-host competitive ability hantavirus deer mouse Host P P PPP PPPPP P P P P P P P P P P P virulence transmission P P virulence comp. ability P P

7. Factors Affecting Virulence Some important factors include: - Host density - Host resistance - Mode of transmission - Timing of transmission - Frequency of superinfection - Viability of the pathogen outside host - Environmental disease reservoirs Host P P PPP PPPPP P P P P P P P P P P P P P P P PP Transmission-virulence tradeoff Competitive-virulence tradeoff Take 3 minutes to talk to your neighbor about the following: What factors do you think will affect the success of versus ? Think of environmental factors, conditions in the host population, life history of the pathogen, etc… P P myxoma - rabbit phage - E.coli anthrax sporescholera - copepod

8. The Evolution of Virulence Lecture Outline Introduction to virulence theory Transmission mode experiment Transmission timing experiment Metapopulation experiment Summary

9. 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. -Horizontal: Pathogens move between unrelated hosts. With high partner fidelity (e.g., with vertical transmission), investments made by one partner can pay off in the future with the same partner (or destructive behavior feeds back negatively for both partners). 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. 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.) H H P H PP H P HH HH PP host pathogen VERTICAL TRANSMISSION HORIZONTAL TRANSMISSION t0t0 t1t1 t0t0 t1t1 high partner fidelitylow partner fidelity

10. 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 - Infected bacteria are resistant to further phage attack - Infected bacteria divide at a slower rate than non- infected 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 This is a nice system to explore the evolution of virulence because the mode of transmission can be experimentally controlled. host: E. coli pathogen: filamentous phage host pilus