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The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness
Oxidative damage to DNA is a significant source of mutations in living organisms. While DNA damage must be repaired to maintain the integrity of the genome and cell survival, errors made during DNA repair may contribute to evolution. Previous work has revealed that Campylobacter jejuni growth in the...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812494/ https://www.ncbi.nlm.nih.gov/pubmed/36619995 http://dx.doi.org/10.3389/fmicb.2022.1062464 |
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author | Talukdar, Prabhat K. Crockett, Torin M. Gloss, Lisa M. Huynh, Steven Roberts, Steven A. Turner, Kyrah L. Lewis, Sebastien T. E. Herup-Wheeler, Tristin L. Parker, Craig T. Konkel, Michael E. |
author_facet | Talukdar, Prabhat K. Crockett, Torin M. Gloss, Lisa M. Huynh, Steven Roberts, Steven A. Turner, Kyrah L. Lewis, Sebastien T. E. Herup-Wheeler, Tristin L. Parker, Craig T. Konkel, Michael E. |
author_sort | Talukdar, Prabhat K. |
collection | PubMed |
description | Oxidative damage to DNA is a significant source of mutations in living organisms. While DNA damage must be repaired to maintain the integrity of the genome and cell survival, errors made during DNA repair may contribute to evolution. Previous work has revealed that Campylobacter jejuni growth in the presence of bile salt deoxycholate (DOC) causes an increase in reactive oxygen species and the occurrence of 8-oxo-deoxyguanosine (8-oxo-dG) DNA lesions. The fundamental goal of this project was to determine if C. jejuni growth in a medium containing DOC contributes to DNA mutations that provide a fitness advantage to the bacterium. Co-culture experiments revealed that C. jejuni growth in a DOC-supplemented medium increases the total number of ciprofloxacin-resistant isolates compared to C. jejuni grown in the absence of DOC. We recovered two individual isolates grown in a medium with DOC that had a point mutation in the gene encoding the EptC phosphoethanolamine transferase. Transformants harboring the EptC variant protein showed enhanced resistance to the antimicrobial agent polymyxin B and DOC when compared to an eptC deletion mutant or the isolate complemented with a wild-type copy of the gene. Finally, we found that the base excision repair (BER), homologous recombination repair (HRR), and nucleotide excision repair (NER) are involved in general oxidative damage repair in C. jejuni but that the BER pathway plays the primary role in the repair of the 8-oxo-dG lesion. We postulate that bile salts drive C. jejuni mutations (adaptations) and enhance bacterial fitness in animals. |
format | Online Article Text |
id | pubmed-9812494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98124942023-01-05 The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness Talukdar, Prabhat K. Crockett, Torin M. Gloss, Lisa M. Huynh, Steven Roberts, Steven A. Turner, Kyrah L. Lewis, Sebastien T. E. Herup-Wheeler, Tristin L. Parker, Craig T. Konkel, Michael E. Front Microbiol Microbiology Oxidative damage to DNA is a significant source of mutations in living organisms. While DNA damage must be repaired to maintain the integrity of the genome and cell survival, errors made during DNA repair may contribute to evolution. Previous work has revealed that Campylobacter jejuni growth in the presence of bile salt deoxycholate (DOC) causes an increase in reactive oxygen species and the occurrence of 8-oxo-deoxyguanosine (8-oxo-dG) DNA lesions. The fundamental goal of this project was to determine if C. jejuni growth in a medium containing DOC contributes to DNA mutations that provide a fitness advantage to the bacterium. Co-culture experiments revealed that C. jejuni growth in a DOC-supplemented medium increases the total number of ciprofloxacin-resistant isolates compared to C. jejuni grown in the absence of DOC. We recovered two individual isolates grown in a medium with DOC that had a point mutation in the gene encoding the EptC phosphoethanolamine transferase. Transformants harboring the EptC variant protein showed enhanced resistance to the antimicrobial agent polymyxin B and DOC when compared to an eptC deletion mutant or the isolate complemented with a wild-type copy of the gene. Finally, we found that the base excision repair (BER), homologous recombination repair (HRR), and nucleotide excision repair (NER) are involved in general oxidative damage repair in C. jejuni but that the BER pathway plays the primary role in the repair of the 8-oxo-dG lesion. We postulate that bile salts drive C. jejuni mutations (adaptations) and enhance bacterial fitness in animals. Frontiers Media S.A. 2022-12-21 /pmc/articles/PMC9812494/ /pubmed/36619995 http://dx.doi.org/10.3389/fmicb.2022.1062464 Text en Copyright © 2022 Talukdar, Crockett, Gloss, Huynh, Roberts, Turner, Lewis, Herup-Wheeler, Parker and Konkel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Talukdar, Prabhat K. Crockett, Torin M. Gloss, Lisa M. Huynh, Steven Roberts, Steven A. Turner, Kyrah L. Lewis, Sebastien T. E. Herup-Wheeler, Tristin L. Parker, Craig T. Konkel, Michael E. The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness |
title | The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness |
title_full | The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness |
title_fullStr | The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness |
title_full_unstemmed | The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness |
title_short | The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness |
title_sort | bile salt deoxycholate induces campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9812494/ https://www.ncbi.nlm.nih.gov/pubmed/36619995 http://dx.doi.org/10.3389/fmicb.2022.1062464 |
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