title: Do Bacterial "Virulence Factors" Always Increase Virulence? A Meta-Analysis of Pyoverdine Production inPseudomonas aeruginosaAs a Test Case.
abstract: Bacterial traits that contribute to disease are termed "virulence factors" and there is much interest in therapeutic approaches that disrupt such traits. What remains less clear is whether a virulence factor identified as such in a particular context is also important in infections involving different host and pathogen types. Here, we address this question using a meta-analytic approach. We statistically analyzed the infection outcomes of 81 experiments associated with one well-studied virulence factor-pyoverdine, an iron-scavenging compound secreted by the opportunistic pathogenPseudomonas aeruginosa. We found that this factor is consistently involved with virulence across different infection contexts. However, the magnitude of the effect of pyoverdine on virulence varied considerably. Moreover, its effect on virulence was relatively minor in many cases, suggesting that pyoverdine is not indispensable in infections. Our works supports theoretical models from ecology predicting that disease severity is multifactorial and context dependent, a fact that might complicate our efforts to identify the most important virulence factors. More generally, our study highlights how comparative approaches can be used to quantify the magnitude and general importance of virulence factors, key knowledge informing future anti-virulence treatment strategies.
authors.affiliation: Department of Plant and Microbial Biology, University of Zurich Zurich, Switzerland.
authors.forename: Elisa T
authors.initials: ET
authors.lastname: Granato
authors.affiliation: School of Life Sciences, University of Warwick Coventry, UK.
authors.forename: Freya
authors.initials: F
authors.lastname: Harrison
authors.affiliation: Department of Plant and Microbial Biology, University of Zurich Zurich, Switzerland.
authors.forename: Rolf
authors.initials: R
authors.lastname: Kümmerli
authors.affiliation: Department of Plant and Microbial Biology, University of ZurichZurich, Switzerland; SIB Swiss Institute of BioinformaticsLausanne, Switzerland.
authors.forename: Adin
authors.initials: A
authors.lastname: Ross-Gillespie
keywords: meta-analysis; pyoverdine; siderophore; virulence; virulence factor