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Manipulating virulence factor availability can have complex consequences for infections


Weigert, Michael; Ross-Gillespie, Adin; Leinweber, Anne; Pessi, Gabriella; Brown, Sam P; Kümmerli, Rolf (2017). Manipulating virulence factor availability can have complex consequences for infections. Evolutionary Applications, 10(1):91-101.

Abstract

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 nonlinear 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 behaviour, 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.

Abstract

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 nonlinear 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 behaviour, 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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Plant and Microbial Biology
Dewey Decimal Classification:580 Plants (Botany)
Language:English
Date:January 2017
Deposited On:08 Jan 2018 20:00
Last Modified:19 Feb 2018 10:04
Publisher:Wiley Open Access
ISSN:1752-4571
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/eva.12431
PubMed ID:28035238

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