Full text

Turn on search term navigation

© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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 antivirulence therapies will ultimately require deeper engagement with the intrinsic complexity of host–pathogen systems.

Details

Title
Manipulating virulence factor availability can have complex consequences for infections
Author
Weigert, Michael 1 ; Ross-Gillespie, Adin 2 ; Leinweber, Anne 3 ; Pessi, Gabriella 3 ; Brown, Sam P 4 ; Kümmerli, Rolf 3 

 Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland; Microbiology, Department of Biology I, Ludwig Maximilians University Munich, Martinsried, Germany 
 Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland; Bioinformatics Core Facility, SIB Swiss Institute of Bioinformatics, Lausanne, Switzerland 
 Department of Plant and Microbial Biology, University of Zurich, Zurich, Switzerland 
 School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, USA 
Pages
91-101
Section
ORIGINAL ARTICLES
Publication year
2017
Publication date
Jan 2017
Publisher
John Wiley & Sons, Inc.
e-ISSN
17524571
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2290116937
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.