Phage–phage competition and biofilms affect interactions between two virulent bacteriophages and <i>Pseudomonas aeruginosa</i>

Virulent bacteriophages (or phages) are viruses that specifically infect and lyse a bacterial host. When multiple phages co-infect a bacterial host, the extent of lysis and dynamics of bacteria-phage and phage-phage interactions are expected to vary. The objective of this study is to identify the factors influencing the interaction of two virulent phages with different Pseudomonas aeruginosa growth states (planktonic, an infected epithelial cell line, and biofilm) by measuring the bacterial time-kill and individual phage replication kinetics. A single administration of phages effectively reduced P. aeruginosa viability in planktonic conditions and infected human lung cell cultures, but phage-resistant variants subsequently emerged. In static biofilms, the phage combination displayed initial inhibition of biofilm dispersal, but sustained control was achieved only by combining phages and the meropenem antibiotic. In contrast, adherent biofilms showed tolerance to phage and/or meropenem, suggesting a spatio-temporal variation in the phage-bacterial interaction. The kinetics of adsorption of each phage to P. aeruginosa during single or co-administration were comparable. However, the phage with the shorter lysis time depleted bacterial resources early and selected a specific nucleotide polymorphism that conferred a competitive disadvantage and cross-resistance to the second phage. The extent and strength of this phage-phage competition and genetic loci conferring phage resistance are, however, P. aeruginosa genotype-dependent. Nevertheless, adding phages sequentially resulted in their unimpeded replication with no significant increase in bacterial host lysis. These results highlight the interrelatedness of phage-phage competition, phage resistance, and specific bacterial growth state (planktonic/biofilm) in shaping the interplay among P. aeruginosa and virulent phages.

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Publication Details

Journal
The ISME Journal
Published
2025-01-01
DOI
https://doi.org/10.1093/ismejo/wraf065
Citations
14
Primary Topic
Bacteriophages and microbial interactions
Type
article
Field-Weighted Citation Impact
24.03

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article

Phage–phage competition and biofilms affect interactions between two virulent bacteriophages and Pseudomonas aeruginosa

Anne Lippegaus, Sandra-Maria Wienhold, Sebastian Krautwurst, Andreas C. Hocke et al.
14 citations
The ISME Journal
Bacteriophages and microbial interactions
24.03
article

Phage–phage competition and biofilms affect interactions between two virulent bacteriophages and Pseudomonas aeruginosa

Anne Lippegaus, Sandra-Maria Wienhold, Sebastian Krautwurst, Andreas C. Hocke, Jean-Damien Ricard, Geraldine Nouailles, Chantal Weissfuss, Krishnamoorthy Gopinath, Magdalena Bürkle, Martin Witzenrath, Baptiste Gaborieau, Kai Papenfort, Laurent Debarbieux, Christine H. Rohde, Imke H. E. Korf, Jean‐Marc Ghigo, Xavière Menatong Tene
article en
14 citations

Abstract

Virulent bacteriophages (or phages) are viruses that specifically infect and lyse a bacterial host. When multiple phages co-infect a bacterial host, the extent of lysis and dynamics of bacteria-phage and phage-phage interactions are expected to vary. The objective of this study is to identify the factors influencing the interaction of two virulent phages with different Pseudomonas aeruginosa growth states (planktonic, an infected epithelial cell line, and biofilm) by measuring the bacterial time-kill and individual phage replication kinetics. A single administration of phages effectively reduced P. aeruginosa viability in planktonic conditions and infected human lung cell cultures, but phage-resistant variants subsequently emerged. In static biofilms, the phage combination displayed initial inhibition of biofilm dispersal, but sustained control was achieved only by combining phages and the meropenem antibiotic. In contrast, adherent biofilms showed tolerance to phage and/or meropenem, suggesting a spatio-temporal variation in the phage-bacterial interaction. The kinetics of adsorption of each phage to P. aeruginosa during single or co-administration were comparable. However, the phage with the shorter lysis time depleted bacterial resources early and selected a specific nucleotide polymorphism that conferred a competitive disadvantage and cross-resistance to the second phage. The extent and strength of this phage-phage competition and genetic loci conferring phage resistance are, however, P. aeruginosa genotype-dependent. Nevertheless, adding phages sequentially resulted in their unimpeded replication with no significant increase in bacterial host lysis. These results highlight the interrelatedness of phage-phage competition, phage resistance, and specific bacterial growth state (planktonic/biofilm) in shaping the interplay among P. aeruginosa and virulent phages.

The ISME JournalVol. 19(1)
Centre National de la Recherche Scientifique (FR), Inserm (FR), Institut Pasteur (FR), Schiller International University (FR), Université Paris Cité (FR), Humboldt-Universität zu Berlin (DE), Hôpital Louis-Mourier (FR), Sorbonne Paris Cité (FR), Fraunhofer Institute for Toxicology and Experimental Medicine (DE), Czech Academy of Sciences, Institute of Microbiology (CZ), German Center for Lung Research (DE), Pharmaceutical Biotechnology (Czechia) (CZ), Freie Universität Berlin (DE), Friedrich Schiller University Jena (DE), Charité - Universitätsmedizin Berlin (DE), Leibniz Institute DSMZ – German Collection of Microorganisms and Cell Cultures (DE)
Infrastructures en Biologie Santé et Agronomie, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, Bundesministerium für Bildung und Forschung
Openalex Percentile: Top 0%
Bacteriophages and microbial interactions
24.03
DOIOpen Access PDFOpenAlex
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