Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replication

ABSTRACT Phages have been shown to use diverse strategies to commandeer bacterial host cell metabolism during infection. However, for many of the physiological changes in bacteria during infection, it is often unclear if they are part of a bacterial response to infection or if they are actively driv...

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Main Authors: Alexa D. Fitzpatrick, Véronique L. Taylor, Pramalkumar H. Patel, Dominick R. Faith, Patrick R. Secor, Karen L. Maxwell
Format: Article
Language:English
Published: American Society for Microbiology 2025-03-01
Series:mBio
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Online Access:https://journals.asm.org/doi/10.1128/mbio.02466-24
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author Alexa D. Fitzpatrick
Véronique L. Taylor
Pramalkumar H. Patel
Dominick R. Faith
Patrick R. Secor
Karen L. Maxwell
author_facet Alexa D. Fitzpatrick
Véronique L. Taylor
Pramalkumar H. Patel
Dominick R. Faith
Patrick R. Secor
Karen L. Maxwell
author_sort Alexa D. Fitzpatrick
collection DOAJ
description ABSTRACT Phages have been shown to use diverse strategies to commandeer bacterial host cell metabolism during infection. However, for many of the physiological changes in bacteria during infection, it is often unclear if they are part of a bacterial response to infection or if they are actively driven by the phage itself. Here, we identify two phage proteins that promote efficient phage replication by reprogramming host amino acid metabolism. These proteins, Eht1 and Eht2, are expressed early in the infection cycle and increase the levels of key amino acids and the arginine-derived polyamine putrescine. This provides a fitness advantage as these metabolites are important for phage replication and are often depleted during infection. We provide evidence that Eht1 and Eht2 alter the expression of bacterial host metabolic genes, and their activities may impinge on metabolism-related signaling processes. This work provides new insight into how phages ensure access to essential host resources during infection and the competitive advantage this provides.IMPORTANCEBacterial viruses, known as phages, are abundant in all environments that are inhabited by bacteria. During the infection process, phages exploit bacterial resources, resulting in notable changes to bacterial metabolism. However, precise mechanisms underlying these changes, and if they are driven by the phage or are a generalized bacterial response to infection, remain poorly understood. We characterized two proteins in Pseudomonas aeruginosa phage JBD44 whose activities alter bacterial host metabolism to optimize phage replication. Our work provides insight into how phages control bacterial processes to ensure access to essential host resources during infection.
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spelling doaj-art-e9e610ddcfc147d399aa3c8ad7bbb8782025-08-20T02:59:06ZengAmerican Society for MicrobiologymBio2150-75112025-03-0116310.1128/mbio.02466-24Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replicationAlexa D. Fitzpatrick0Véronique L. Taylor1Pramalkumar H. Patel2Dominick R. Faith3Patrick R. Secor4Karen L. Maxwell5Department of Biochemistry, University of Toronto, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, CanadaDepartment of Biochemistry, University of Toronto, Toronto, CanadaDepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USADepartment of Microbiology and Cell Biology, Montana State University, Bozeman, Montana, USADepartment of Biochemistry, University of Toronto, Toronto, CanadaABSTRACT Phages have been shown to use diverse strategies to commandeer bacterial host cell metabolism during infection. However, for many of the physiological changes in bacteria during infection, it is often unclear if they are part of a bacterial response to infection or if they are actively driven by the phage itself. Here, we identify two phage proteins that promote efficient phage replication by reprogramming host amino acid metabolism. These proteins, Eht1 and Eht2, are expressed early in the infection cycle and increase the levels of key amino acids and the arginine-derived polyamine putrescine. This provides a fitness advantage as these metabolites are important for phage replication and are often depleted during infection. We provide evidence that Eht1 and Eht2 alter the expression of bacterial host metabolic genes, and their activities may impinge on metabolism-related signaling processes. This work provides new insight into how phages ensure access to essential host resources during infection and the competitive advantage this provides.IMPORTANCEBacterial viruses, known as phages, are abundant in all environments that are inhabited by bacteria. During the infection process, phages exploit bacterial resources, resulting in notable changes to bacterial metabolism. However, precise mechanisms underlying these changes, and if they are driven by the phage or are a generalized bacterial response to infection, remain poorly understood. We characterized two proteins in Pseudomonas aeruginosa phage JBD44 whose activities alter bacterial host metabolism to optimize phage replication. Our work provides insight into how phages control bacterial processes to ensure access to essential host resources during infection.https://journals.asm.org/doi/10.1128/mbio.02466-24phage infectionbacterial metabolismbiofilmPseudomonas aeruginosa
spellingShingle Alexa D. Fitzpatrick
Véronique L. Taylor
Pramalkumar H. Patel
Dominick R. Faith
Patrick R. Secor
Karen L. Maxwell
Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replication
mBio
phage infection
bacterial metabolism
biofilm
Pseudomonas aeruginosa
title Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replication
title_full Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replication
title_fullStr Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replication
title_full_unstemmed Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replication
title_short Phage reprogramming of Pseudomonas aeruginosa amino acid metabolism drives efficient phage replication
title_sort phage reprogramming of pseudomonas aeruginosa amino acid metabolism drives efficient phage replication
topic phage infection
bacterial metabolism
biofilm
Pseudomonas aeruginosa
url https://journals.asm.org/doi/10.1128/mbio.02466-24
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