Two papers demonstrate empirical evidence for related models predicting the origin of virulence

Virulence is an abstraction of the harm caused to hosts by a pathogen, and explaining the paradox of virulence has been an active field of study in evolution for a while. Indeed, being interesting to people who want virulence to go away, its a way to both study evolution and get paid. In general the harm caused to the hosts of pathogens is not great for the pathogen, after all, why hurt or lose a useful host? However, in studying the abstraction with basic research, we’ve found that virulence is almost always is part of helping the pathogen find a new host. Thus the generalized answer to the paradox is that so long as the harm to the host causes the parasite to spread effectively enough, it doesn’t really matter how much harm is caused to the host – as the parasite will have already found new hosts to spread from. At the same time, helpful bacteria don’t have nearly the same need to spread as pathogenic ones, as they keep their hosts happy and alive and can stick around for longer.

Here I’ll introduce two papers demonstrating this model and try to convince you of how important it is.

 

The spectrum between virulence and mutualism can be seen as a trade off between two strategies, as well as of course often a mix between the two. A critter existing in community with another one can care little for its host and work to be as infectious as possible at the host’s expense, thus increasing virulence. In this strategy it doesn’t matter so much that the host becomes quickly unsuitable so long as the parasite has already found replacement hosts sneezed on, or transmitted to, by the time that happens. Or it can do the opposite and try its best to reduce impact on the host, spread infectious particles slowly or even not at all, and thus not need to spread too quickly because it will last a while in each host. Most of the critters that live in our guts and on our skin are at this end of the spectrum, and have become so adept at not messing up their host as to actually benefit us in some way. On the other end of the spectrum are parasitoids. These are the parasites that not only destroy their host in their race to infect as many more hosts as possible, but spend the majority of their life cycle doing so and ultimately sterilize or kill, and sometimes consume the host in the process. The Xenomorphs from the movie Alien are a beautiful example of a bunch of these sorts of parasitiod strategies, each inspired by real terrifying stuff in nature. This might all seem uselessly theoretical, but the implications it has for public health are really cool.

Before the advent of antibiotics, we lived with Staphylococcus aureus strains on our skin that existed in a complex mixture of commensal and virulent strategies, but antibiotics suddenly applied very strong selective pressure against any vaguely virulent strategy. Thus, following the model, the observed sudden decrease in both virulence and transmissibility of virulent strains makes a lot of sense. However, the sudden increase in both virulence and transmissibility of virulent strains that we’ve seen in multi-drug resistant (MRSA) strains also makes sense. Indeed, if you look back far enough in the literature all of the crazy new and terrible virulence factors we are now seeing in MRSA strains all existed before the 1930s. For example, while the pyomyositis and necrotizing pneumonia we are now seeing is commonly associated with poverty, tropical climates and HIV, ie: things which didn’t get much attention prior to 1935, it was described. (At lest with this source you’ll need to wade your way past the kinds of phrases that start with “Africans are not different from any other humans, however, …” to page 1214) Until recently it would not be terribly remarkable, being easily addressed with a simple round of I.V. antibiotics.  Additionally, the PVL toxin which that first paper describes as now being found in pneumonia was initially discovered by Van deVelde in 1894 and was named after Sir Philip Noel Panton and Francis Valentine when they associated it with soft tissue infections in 1932. All of this makes logical sense anyhow, the mechanisms of antibiotic resistance are not associated with pathogenesis.

Timing of transmission and the evolution of virulence of an insect virus.

JC de Roode, AJ Yates, & S Altizer. Published 2002 in Proc. R. Soc. Lond. B doi:10.1098/rspb.2002.1976

We used the nuclear polyhedrosis virus of the gypsy moth, Lymantria dispar, to investigate whether the timing of transmission influences the evolution of virulence. In theory, early transmission should favour rapid replication and increase virulence, while late transmission should favour slower replication and reduce virulence. We tested this prediction by subjecting one set of 10 virus lineages to early transmission (Early viruses) and another set to late transmission (Late viruses). Each lineage of virus underwent nine cycles of transmission. Virulence assays on these lineages indicated that viruses transmitted early were significantly more lethal than those transmitted late. Increased exploitation of the host appears to come at a cost, however. While Early viruses initially produced more progeny, Late viruses were ultimately more productive over the entire duration of the infection. These results illustrate fitness trade-offs associated with the evolution of virulence and indicate that milder viruses can obtain a numerical advantage when mild and harmful strains tend to infect separate hosts.

Virulence-transmission trade-offs and population divergence in virulence in a naturally occurring butterfly parasite (PDF).

VS Cooper, MH Reiskind, et al. Published 2002 in PNAS doi:10.1073/pnas.0710909105

Why do parasites harm their hosts? Conventional wisdom holds that because parasites depend on their hosts for survival and transmission, they should evolve to become benign, yet many parasites cause harm. Theory predicts that parasites could evolve virulence (i.e., parasite-induced reductions in host fitness) by balancing the transmission benefits of parasite replication with the costs of host death. This idea has led researchers to predict how human interventions—such as vaccines—may alter virulence evolution, yet empirical support is critically lacking. We studied a protozoan parasite of monarch butterflies and found that higher levels of within-host replication resulted in both higher virulence and greater transmission, thus lending support to the idea that selection for parasite transmission can favor parasite genotypes that cause substantial harm. Parasite fitness was maximized at an intermediate level of parasite replication, beyond which the cost of increased host mortality outweighed the benefit of increased transmission. A separate experiment confirmed genetic relationships between parasite replication and virulence, and showed that parasite genotypes from two monarch populations caused different virulence. These results show that selection on parasite transmission can explain why parasites harm their hosts, and suggest that constraints imposed by host ecology can lead to population divergence in parasite virulence.