Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.

Bacteriophages infect gram-negative bacteria by attaching to molecules present on the bacterial surface, often lipopolysaccharides (LPS). Modification of LPS can lead to resistance to phage infection. In addition, LPS modifications can impact antibiotic susceptibility, allowing for phage-antibiotic...

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Main Authors: Lavisha Parab, Jordan Romeyer Dherbey, Norma Rivera, Michael Schwarz, Jenna Gallie, Frederic Bertels
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3002952
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author Lavisha Parab
Jordan Romeyer Dherbey
Norma Rivera
Michael Schwarz
Jenna Gallie
Frederic Bertels
author_facet Lavisha Parab
Jordan Romeyer Dherbey
Norma Rivera
Michael Schwarz
Jenna Gallie
Frederic Bertels
author_sort Lavisha Parab
collection DOAJ
description Bacteriophages infect gram-negative bacteria by attaching to molecules present on the bacterial surface, often lipopolysaccharides (LPS). Modification of LPS can lead to resistance to phage infection. In addition, LPS modifications can impact antibiotic susceptibility, allowing for phage-antibiotic synergism. The evolutionary mechanism(s) behind such synergistic interactions remain largely unclear. Here, we show that the presence of antibiotics can affect the evolution of resistance to phage infection, using phage ΦX174 and Escherichia coli C. We use a collection of 34 E. coli C LPS strains, each of which is resistant to ΦX174, and has either a "rough" or "deep rough" LPS phenotype. Growth of the bacterial strains with the deep rough phenotype is inhibited at low concentrations of chloramphenicol and, to a much lesser degree, gentamicin. Treating E. coli C wild type with ΦX174 and chloramphenicol eliminates the emergence of mutants with the deep rough phenotype, and thereby slows the evolution of resistance to phage infection. At slightly lower chloramphenicol concentrations, phage resistance rates are similar to those observed at high concentrations; yet, we show that the diversity of possible mutants is much larger than at higher chloramphenicol concentrations. These data suggest that specific antibiotic concentrations can lead to synergistic phage-antibiotic interactions that disappear at higher antibiotic concentrations. Overall, we show that the change in survival of various ΦX174-resistant E. coli C mutants in the presence of antibiotics can explain the observed phage-antibiotic synergism.
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language English
publishDate 2025-01-01
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spelling doaj-art-fc20ae0a0e8b40e08dd8b015e098a1402025-02-05T05:30:17ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-01-01231e300295210.1371/journal.pbio.3002952Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.Lavisha ParabJordan Romeyer DherbeyNorma RiveraMichael SchwarzJenna GallieFrederic BertelsBacteriophages infect gram-negative bacteria by attaching to molecules present on the bacterial surface, often lipopolysaccharides (LPS). Modification of LPS can lead to resistance to phage infection. In addition, LPS modifications can impact antibiotic susceptibility, allowing for phage-antibiotic synergism. The evolutionary mechanism(s) behind such synergistic interactions remain largely unclear. Here, we show that the presence of antibiotics can affect the evolution of resistance to phage infection, using phage ΦX174 and Escherichia coli C. We use a collection of 34 E. coli C LPS strains, each of which is resistant to ΦX174, and has either a "rough" or "deep rough" LPS phenotype. Growth of the bacterial strains with the deep rough phenotype is inhibited at low concentrations of chloramphenicol and, to a much lesser degree, gentamicin. Treating E. coli C wild type with ΦX174 and chloramphenicol eliminates the emergence of mutants with the deep rough phenotype, and thereby slows the evolution of resistance to phage infection. At slightly lower chloramphenicol concentrations, phage resistance rates are similar to those observed at high concentrations; yet, we show that the diversity of possible mutants is much larger than at higher chloramphenicol concentrations. These data suggest that specific antibiotic concentrations can lead to synergistic phage-antibiotic interactions that disappear at higher antibiotic concentrations. Overall, we show that the change in survival of various ΦX174-resistant E. coli C mutants in the presence of antibiotics can explain the observed phage-antibiotic synergism.https://doi.org/10.1371/journal.pbio.3002952
spellingShingle Lavisha Parab
Jordan Romeyer Dherbey
Norma Rivera
Michael Schwarz
Jenna Gallie
Frederic Bertels
Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.
PLoS Biology
title Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.
title_full Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.
title_fullStr Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.
title_full_unstemmed Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.
title_short Chloramphenicol and gentamicin reduce the evolution of resistance to phage ΦX174 by suppressing a subset of E. coli LPS mutants.
title_sort chloramphenicol and gentamicin reduce the evolution of resistance to phage φx174 by suppressing a subset of e coli lps mutants
url https://doi.org/10.1371/journal.pbio.3002952
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