Pf4 Phage Variant Infection Reduces Virulence-Associated Traits in Pseudomonas aeruginosa

Damien Tortuel, Ali Tahrioui, Audrey David, Mélyssa Cambronel, Flore Nilly, Thomas Clamens, Olivier Maillot, Magalie Barreau, Marc G J Feuilloley, Olivier Lesouhaitier, Alain Filloux, Emeline Bouffartigues, Pierre Cornelis, Sylvie Chevalier

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Abstract

Pf4 is a filamentous bacteriophage integrated as a prophage into the genome of Pseudomonas aeruginosa PAO1. Pf4 virions can be produced without killing P. aeruginosa. However, cell lysis can occur during superinfection when Pf virions successfully infect a host lysogenized by a Pf superinfective variant. We have previously shown that infection of P. aeruginosa PAO1 with a superinfective Pf4 variant abolished twitching motility and altered biofilm architecture. More precisely, most of the cells embedded into the biofilm were showing a filamentous morphology, suggesting the activation of the cell envelope stress response involving both AlgU and SigX extracytoplasmic function sigma factors. Here, we show that Pf4 variant infection results in a drastic dysregulation of 3,360 genes representing about 58% of P. aeruginosa genome; of these, 70% of the virulence factors encoding genes show a dysregulation. Accordingly, Pf4 variant infection (termed Pf4*) causes in vivo reduction of P. aeruginosa virulence and decreased production of N-acyl-homoserine lactones and 2-alkyl-4-quinolones quorum-sensing molecules and related virulence factors, such as pyocyanin, elastase, and pyoverdine. In addition, the expression of genes involved in metabolism, including energy generation and iron homeostasis, was affected, suggesting further relationships between virulence and central metabolism. Altogether, these data show that Pf4 phage variant infection results in complex network dysregulation, leading to reducing acute virulence in P. aeruginosa. This study contributes to the comprehension of the bacterial response to filamentous phage infection. IMPORTANCE Filamentous bacteriophages can become superinfective and infect P. aeruginosa, even though they are inserted in the genome as lysogens. Despite this productive infection, growth of the host is only mildly affected, allowing the study of the interaction between the phage and the host, which is not possible in the case of lytic phages killing rapidly their host. Here, we demonstrate by transcriptome and phenotypic analysis that the infection by a superinfective filamentous phage variant causes a massive disruption in gene expression, including those coding for virulence factors and metabolic pathways.

Original languageEnglish
Pages (from-to)e0154822
JournalMicrobiology spectrum
Volume10
Issue number5
Early online date29 Aug 2022
DOIs
Publication statusPublished - Sep 2022

Bibliographical note

Funding Information:
This research was funded by European FEDER funds (FEDER HN0005571), and the University of Rouen Normandy.

Funding Information:
The CBSA lab is supported by the Région Normandie (France), Evreux Portes de Normandie (France), and European FEDER funds. D.T. is supported by grants from the Région Normandie (France), and M.C. and A.D. are supported by grants from the French ministry (MENRT). The funders had no role in study design, data collection and interpretation, or the decision to submit this work for publication. We gratefully acknowledge Paul Williams (Centre for Biomolecular Sciences, University of Nottingham) for providing PAO1 DpqsA CTX-pqsA::lux biosensor strain.

Funding Information:
The CBSA lab is supported by the Région Normandie (France), Evreux Portes de Normandie (France), and European FEDER funds. D.T. is supported by grants from the Région Normandie (France), and M.C. and A.D. are supported by grants from the French ministry (MENRT). The funders had no role in study design, data collection and interpretation, or the decision to submit this work for publication. We gratefully acknowledge Paul Williams (Centre for Biomolecular Sciences, University of Nottingham) for providing PAO1 DpqsA CTX-pqsA::lux biosensor strain. We declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. D.T. realized most of the experiments, analyzed the data, and wrote the first manuscript draft. A.T., A.D., M.C., F.N., and T.C. contributed to the experiments and data interpretations. O.M. and M.B. provided technical assistance. M.G.J.F., O.L., and A.F. revised the manuscript. E.B. and S.C. led and coordinated the project. P.C. and S.C. improved the writing of the manuscript. All authors read and approved the final manuscript. This research was funded by European FEDER funds (FEDER HN0005571), and the University of Rouen Normandy.

Publisher Copyright:
Copyright © 2022 Tortuel et al.

Copyright:
Copyright 2022 Elsevier B.V., All rights reserved.

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