Experimental evidence for a new paradigm explaining the evolution of virulence

Traditionally, evolutionary theory has attempted to predict the success of traits through their effect at the cell-level. Virulence traits, when expressed in parasites, act to decrease the fitness of the host, and thus indirectly of the parasite itself. To explain the success of such traits, current evolutionary models must therefore assume a positive correlation between virulence and parasite transmission. Parasite virulence can be selected for as long as debilitation of the present host is compensated by an increase in the number of new hosts becoming infected. Here, I test the ability of such models to explain the apparent success of a plasmid-borne virulence trait (postsegregational killing (PSK)). In contrast to expectations of cell-level models, PSK did not enable host cells, or host plasmids, to replicate more frequently. Despite this, in some environments plasmids encoding PSK were more successful than isogenic ΔPSK counterparts. To explain this finding I present an alternative, 'competition' model. This model proposes that PSK systems are selected at the plasmid-level, by inhibiting the reproduction of competitors, without the need to contribute to cell-level fitness. A mathematical model was written to formalise predictions of this model. Experimental test of these predictions were consistent with the proposal above. I also demonstrate that the competition model can explain the accumulation of PSK systems to the genomes of plasmids. Other commonly plasmid-borne traits (e.g. antibiotic resistance) may also form de-facto PSK systems, rendering a cell 'addicted' to an otherwise dispensable element. If so, an understanding of how plasmid-level competition influences their selection may be essential to models hoping to predict their success and evolution. In support of this interpretation, I demonstrate the ability of plasmids to undergo plasmid-level competition in environments inhibiting cell-level reproduction