Adin Ross-Gillespie | Search bioRxiv

bioRxiv2016

Manipulating virulence factor availability can have complex consequences for infections

Given the rise of bacterial resistance against antibiotics, we urgently need alternative strategies to fight infections. Some propose we should disarm rather than kill bacteria, through targeted disruption of their virulence factors. It is assumed that this approach (i) induces weak selection for resistance because it should only minimally impact bacterial fitness, and (ii) is specific, only interfering with the virulence factor in question. Given that pathogenicity emerges from complex interactions between pathogens, hosts, and their environment, such assumptions may be unrealistic. To address this issue in a test case, we conducted experiments with the opportunistic human pathogen Pseudomonas aeruginosa, where we manipulated the availability of a virulence factor, the iron-scavenging pyoverdine, within the insect host Galleria mellonella. We observed that pyoverdine availability was not stringently predictive of virulence, and affected bacterial fitness in non-linear ways. We show that this complexity could partly arise because pyoverdine availability affects host responses and alters the expression of regulatorily linked virulence factors. Our results reveal that virulence-factor manipulation feeds back on pathogen and host behavior, which in turn affects virulence. Our findings highlight that realizing effective and evolutionarily robust anti-virulence therapies will ultimately require deeper engagement with the intrinsic complexity of host-pathogen systems.

Evolutionary Biology↗

bioRxiv2016

When is a bacterial "virulence factor" really virulent?

Bacterial traits that contribute to disease are termed virulence factors and there is much interest in therapeutic approaches that disrupt such traits. However, ecological theory predicts disease severity to be multifactorial and context dependent, which might complicate our efforts to identify the most generally important virulence factors. Here, we use meta-analysis to quantify disease outcomes associated with one well-studied virulence factor - pyoverdine, an iron-scavenging compound secreted by the opportunistic pathogen Pseudomonas aeruginosa. Consistent with ecological theory, we found that the effect of pyoverdine, albeit frequently contributing to disease, varied considerably across infection models. In many cases its effect was relatively minor, suggesting that pyoverdine is rarely essential for infections. Our work demonstrates the utility of meta-analysis as a tool to quantify variation and overall effects of purported virulence factors across different infection models. This standardised approach will help us to evaluate promising targets for anti-virulence approaches.

Microbiology↗