Abstract
The increasing prevalence of antimicrobial resistance and the limited availability of new antimicrobial agents have created an urgent need for new approaches to combat these issues. One such approach involves reevaluating the use of old antibiotics to ensure their appropriate usage and maximize their effectiveness, as older antibiotics could help alleviate the burden on newer agents. An example of such an antibiotic is chloramphenicol (CHL), which is rarely used due to its hematological toxicity. In the current study, we employed a previously published transposon mutant library in MG1655/pTF2::blaCTX-M-1, containing over 315,000 unique transposon insertions, to identify the genetic factors that play an important role during growth in the presence of CHL. The list of conditionally essential genes, collectively referred to as the secondary resistome (SR), included 67 genes. To validate our findings, we conducted gene knockout experiments on six genes: arcA, hfq, acrZ, cls, mdfA, and nlpI. Deleting these genes resulted in increased susceptibility to CHL as demonstrated by MIC estimations and growth experiments, suggesting that targeting the products encoded from these genes may reduce the dose of CHL needed for treatment and hence reduce the toxicity associated with CHL treatment. Thus, the gene products are indicated as targets for antibiotic adjuvants to favor the use of CHL in modern medicine.
Originalsprog | Engelsk |
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Artikelnummer | 73 |
Tidsskrift | Antibiotics |
Vol/bind | 13 |
Udgave nummer | 1 |
Antal sider | 14 |
ISSN | 2079-6382 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:The authors would like to thank the staff at the GeoGenetics Sequencing Core at the Globe Institute, University of Copenhagen for their authorization to use Covaris M220 to shear the DNA. V.G. acknowledges the Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia for her post-doctoral grants (Grant Numbers ED481B-2018-018 and ED481D-2022-012). A.H.-F. is supported by a grant from the “Ministerio de Universidades”, Spain (BG22/00150—Beatriz Galindo program).
Funding Information:
This research was funded by a PhD scholarship from King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) (grant number SO/3289/2012) via the Saudi Arabian Cultural Office.
Publisher Copyright:
© 2024 by the authors.