Abstract
Host resistance through immune clearance is predicted to favor pathogens that are able to transmit faster and are hence more virulent. Increasing pathogen virulence is, in turn, typically assumed to be mediated by increasing replication rates. However, experiments designed to test how pathogen virulence and replication rates evolve in response to increasing host resistance, as well as the relationship between the two, are rare and lacking for naturally evolving host-pathogen interactions. We inoculated 55 isolates of Mycoplasma gallisepticum, collected over 20 y from outbreak, into house finches (Haemorhous mexicanus) from disease-unexposed populations, which have not evolved protective immunity to M. gallisepticum We show using 3 different metrics of virulence (body mass loss, symptom severity, and putative mortality rate) that virulence has increased linearly over >150,000 bacterial generations since outbreak (1994 to 2015). By contrast, while replication rates increased from outbreak to the initial spread of resistance (1994 to 2004), no further increases have occurred subsequently (2007 to 2015). Finally, as a consequence, we found that any potential mediating effect of replication rate on virulence evolution was restricted to the period when host resistance was initially increasing in the population. Taken together, our results show that pathogen virulence and replication rates can evolve independently, particularly after the initial spread of host resistance. We hypothesize that the evolution of pathogen virulence can be driven primarily by processes such as immune manipulation after resistance spreads in host populations.
Highlights
Field tests of the impacts of host resistance on pathogen virulence and replication rates are more challenging because there are few host–pathogen systems for which we have documented natural changes in host resistance and associated changes in pathogen virulence over time [18,19,20,21]
Our results show that the virulence of M. gallisepticum has increased linearly from outbreak (1994), through the spread of house finch resistance, to the present day (2015)
In contrast to linear increases in virulence, pathogen loads and replication rate displayed significant quadratic relationships with year of isolate sampling, with pathogen load and replication rate increasing from disease outbreak to the spread of host resistance, but not thereafter
Summary
Field tests of the impacts of host resistance on pathogen virulence and replication rates are more challenging because there are few host–pathogen systems for which we have documented natural changes in host resistance and associated changes in pathogen virulence over time [18,19,20,21]. Host resistance can be manipulated through either vaccination with a recombinant antigen or wholeparasite immunization, with pathogen responses quantified after passage through resistant versus susceptible hosts Using such approaches, the rodent malaria model Plasmodium chabaudi was shown to evolve increased virulence when repeatedly passaged through either vaccinated or immunized mice [16, 17]. Whether differences in the effectiveness of the immune responses elicited can explain differences between these findings is unknown Regardless, these studies demonstrate that experimental increases in host resistance can drive virulence evolution, as predicted by theory; for some reason, this association only emerges from increased replication rates in vaccinated hosts [16, 17]
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