The Impact of Pf Bacteriophages on the Fitness of<i>Pseudomonas aeruginosa</i>; A Mathematical Modeling Approach

Abstract Pseudomonas aeruginosa(Pa) is a major bacterial pathogen responsible for chronic lung infections in cystic fibrosis patients. Recent work by ourselves and others has implicated Pf bacteriophages, non-lytic filamentous viruses produced byPa, in the chronicity and severity ofPainfections. Pf phages act as structural elements inPabiofilms and sequester aerosolized antibiotics, thereby contributing to antibiotic tolerance. Consistent with a selective advantage in this setting, the prevalence of Pf+ bacteria increases over time in these patients. However, the production of Pf phages comes at a metabolic cost to bacteria, such that Pf+ strains grow more slowly than Pf- strains in vitro. Here, we use a mathematical model to investigate how these competing pressures might influence the relative abundance of Pf+ versus Pf- strains in different settings. Our model predicts that Pf+ strains ofPacan only outcompete Pf- strains if the benefits of phage production falls solely onto Pf+ strains and not onto the overall bacterial community in the lung. Further, phage production only leads to a net positive gain in fitness at antibiotic concentrations slightly above the minimum inhibitory concentration (i.e., concentrations for which the benefits of antibiotic sequestration outweigh the metabolic cost of phage production), but which are not lethal for Pf+ strains. As a result, our model predicts that frequent administration of intermediate doses of antibiotics with low decay rates favors Pf+ over Pf- strains. These models inform our understanding of the ecology of Pf phages and suggest potential treatment strategies for Pf+Painfections.Importance Filamentous phages are a frontier in bacterial pathogenesis, but the impact of these phages on bacterial fitness is unclear. In particular, Pf phages produced byPapromote antibiotic tolerance but are metabolically expensive to produce, suggesting that competing pressures may influence the prevalence of Pf+ versus Pf- strains ofPain different settings. Our results identify conditions likely to favor Pf+ strains and thus antibiotic tolerance. This study contributes to a better understanding of the unique ecology of filamentous phages and may facilitate improved treatment strategies for combating antibiotic tolerance..

Medienart:	Preprint

Erscheinungsjahr:	2022
Erschienen:	2022

Enthalten in:	bioRxiv.org - (2022) vom: 11. Nov. Zur Gesamtaufnahme - year:2022

Sprache:	Englisch

Beteiligte Personen:	Pourtois, Julie D. [VerfasserIn] Kratochvil, Michael J. [VerfasserIn] Chen, Qingquan [VerfasserIn] Haddock, Naomi L. [VerfasserIn] Burgener, Elizabeth B. [VerfasserIn] De Leo, Giulio A. [VerfasserIn] Bollyky, Paul L. [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	570 Biology

doi:	10.1101/2020.08.30.272203

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PPN (Katalog-ID):	XBI018655033