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  Chloramphenicol reduces phage resistance evolution by suppressing bacterial cell surface mutants

Parab, L., Romeyer Dherbey, J., Rivera, N., Schwarz, M., & Bertels, F. (submitted). Chloramphenicol reduces phage resistance evolution by suppressing bacterial cell surface mutants.

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 Creators:
Parab, Lavisha1, Author           
Romeyer Dherbey, Jordan1, Author           
Rivera, Norma, Author
Schwarz, Michael2, Author           
Bertels, Frederic3, Author                 
Affiliations:
1IMPRS for Evolutionary Biology, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445639              
2Department Microbial Population Biology (Rainey), Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_2421699              
3Research Group Microbial Molecular Evolution (Bertels), Department Microbial Population Biology (Rainey), Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_2497692              

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Free keywords: antibiotic resistance, phage resistance, evolutionary rescue, fluctuation assay
 Abstract: Bacteriophages infect Gram-negative bacteria by attaching to molecules present on the bacterial outer membrane, often lipopolysaccharides (LPS). Modification of the LPS can lead to phage resistance. LPS modifications also impact antibiotic susceptibility, allowing for phage-antibiotic synergism. The mechanism for these synergistic interactions is unclear. Here, we show that antibiotics affect the evolution of phage resistance using phage ΦX174 and Escherichia coli C wildtype. We use a collection of E. coli C LPS mutants, each of which is resistant to ΦX174, and has either a “rough” or “deep-rough” LPS phenotype. Growth of deep rough mutants is inhibited at subinhibitory chloramphenicol concentrations. In contrast, gentamicin has no major effect on growth. Hypothesis testing shows that treating E. coli C wildtype with ΦX174 and chloramphenicol eliminates deep rough mutants, and reduces phage resistance evolution. Our results show that differential survival of phage resistant mutants with antibiotics explains phage-antibiotic synergism in our model system.

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Language(s): eng - English
 Dates: 2023-08-282023
 Publication Status: Submitted
 Pages: 33
 Publishing info: -
 Table of Contents: -
 Rev. Type: No review
 Identifiers: DOI: 10.1101/2023.08.28.552763
 Degree: -

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