The bile salt deoxycholate induces Campylobacter jejuni genetic point mutations that promote increased antibiotic resistance and fitness

• Published in: Frontiers in microbiology Vol. 13; p. 1062464
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21-12-2022
• Subjects: DNA lesions; DNA repair; fluoroquinolone resistance; Microbiology; reactive oxygen species; sodium deoxycholate; sodium deoxycholate; DNA lesions; DNA repair; fluoroquinolone resistance; reactive oxygen species
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2022.1062464

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
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
growth in a medium containing DOC contributes to DNA mutations that provide a fitness advantage to the bacterium. Co-culture experiments revealed that
growth in a DOC-supplemented medium increases the total number of ciprofloxacin-resistant isolates compared to
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
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
but that the BER pathway plays the primary role in the repair of the 8-oxo-dG lesion. We postulate that bile salts drive
mutations (adaptations) and enhance bacterial fitness in animals.