Resistance development in Escherichia coli to delafloxacin at pHs 6.0 and 7.3 compared to ciprofloxacin

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dc.contributor.author Bösch, A
dc.contributor.author Macha, M.E
dc.contributor.author Ren, Q
dc.contributor.author Kohler, P
dc.contributor.author Qi, W
dc.contributor.author Flury, B.B
dc.date.accessioned 2024-06-18T10:43:16Z
dc.date.available 2024-06-18T10:43:16Z
dc.date.issued 2023-10-26
dc.identifier.citation Bösch A, Macha ME, Ren Q, Kohler P, Qi W, Babouee Flury B. Resistance development in Escherichia coli to delafloxacin at pHs 6.0 and 7.3 compared to ciprofloxacin. Antimicrobial Agents and Chemotherapy. 2023 Nov 15;67(11):e01625-22. en_US
dc.identifier.uri http://41.93.38.5:8080/xmlui/handle/123456789/57
dc.description.abstract Understanding the resistance mechanisms of antibiotics in the micro-environment of the infection is important to assess their clinical applicability and potentially prevent resistance development. We compared the laboratory resistance evolution of Escherichia coli to delafloxacin (DLX) compared to ciprofloxacin (CIP), the co-resistance evolution, and underlying resistance mechanisms at different pHs. Three clones from each of the eight clinical E. coli isolates were subjected to subinhibitory concentrations of DLX or CIP in parallel at either pH 7.3 or 6.0. Minimum inhibitory concentrations (MICs) were regularly tested (at respective pHs), and the antibiotic concentration was adjusted accordingly. After 30 passages, MICs were determined in the presence of the efflux pump inhibitor phenylalanine-arginine-β-naphthylamide. Whole genome sequencing of the parental isolates and their resistant derivatives (n = 54) was performed. Complementation assays were carried out for selected mutations. Quantitative PCR and efflux experiments were carried out for selected derivatives. For DLX-challenged strains, resistance to DLX evolved much slower in acidic than in neutral pH, whereas for CIP-challenged strains, the opposite was the case. Mutations in the quinolone resistance determining region were mainly seen in CIP-challenged E. coli, whereas a multifactorial mechanism including mutations in efflux-related genes played a role in DLX resistance evolution (predominantly at pH 6.0). This work provides novel insights into the resistance mechanisms of E. coli to delafloxacin and highlights the importance of understanding micro-environmental conditions at the infection site that might affect the true clinical efficacy of antibiotics and challenges our current antibiotic susceptibility-testing paradigm. en_US
dc.description.sponsorship Funder Author(s) A. Menarini GmbH Baharak Babouee Flury en_US
dc.language.iso en en_US
dc.publisher American society for microbiology en_US
dc.relation.ispartofseries Antimicrobial agents and Chemotherapy;Volume 67 Issue 11
dc.subject delafloxacin; en_US
dc.subject Escherichia coli; en_US
dc.subject ciprofloxacin; en_US
dc.subject resistance evolution; en_US
dc.subject pH. en_US
dc.title Resistance development in Escherichia coli to delafloxacin at pHs 6.0 and 7.3 compared to ciprofloxacin en_US
dc.type Article en_US


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