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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2025-01-01
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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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id | doaj-art-fc20ae0a0e8b40e08dd8b015e098a140 |
institution | Kabale University |
issn | 1544-9173 1545-7885 |
language | English |
publishDate | 2025-01-01 |
publisher | Public Library of Science (PLoS) |
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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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