Evolution of virulence in opportunistic pathogens: generalism, plasticity, and control

Abstract

Standard virulence evolution theory assumes that virulence factors are maintained because they aid parasitic exploitation, increasing growth within and/or transmission between hosts. An increasing number of studies now demonstrate that many opportunistic pathogens (OPs) do not conform to these assumptions, with virulence factors maintained instead because of advantages in non-parasitic contexts. Here we review virulence evolution theory in the context of OPs and highlight the importance of incorporating environments outside a focal virulence site. We illustrate that virulence selection is constrained by correlations between these external and focal settings and pinpoint drivers of key environmental correlations, with a focus on generalist strategies and phenotypic plasticity. We end with a summary of key theoretical and empirical challenges to be met for a fuller understanding of OPs.

Figure 1

Ecological and evolutionary dynamics of virulence factors across two growth environments. N^A and N^V represent bacterial densities in the asymptomatic and virulence sites, respectively. Arrows represent demographic processes of growth (g, r) and transmission (colonisation c, export e). Red arrows represent a positive selective impact of VF expression. (a) Our basic ecological model (see Box 1 for analysis). (b) Epidemiological selection ; the dominant theoretical paradigm for virulence evolution states that virulence factors yield a net benefit during parasitic exploitation because of positive effects on within-host growth and/or transmission. (c) Purely co-incidental selection . (d) Purely within-host selection .

Figure 2

Adaptation to a benign environment A can pre-adapt an opportunistic pathogen for virulent growth in V if there is a significant positive association between the properties of environments A and V (i.e., if fast growth in A, g, is correlated with fast growth in V, r, or cov(g,r) > 0).

Figure 3

Adaptation to a benign environment A can reduce the capacity for virulent growth in V (and vice versa) if there is a significant negative association (trade-off) between growth rates g and r. (A negative selective impact of virulence factor expression is denoted by the blue arrow.) Plasticity can decouple the trade-off by expressing the V-specific virulence factor (VF) in V and not in A (VF_0,1, where the subscripts denote expression in the two environments). However, plasticity also allows a ‘worst of all worlds’ outcome, VF_1,0, whereby virulence factors are expressed inappropriately (here, only in A).