Genome-wide screen reveals cellular functions that counteract rifampicin lethality in Escherichia coli

Rifamycins are a group of antibiotics with a wide antibacterial spectrum. Although the binding target of rifamycin has been well characterized, the mechanisms underlying the discrepant killing efficacy between gram-negative and gram-positive bacteria remain poorly understood. Using a high-throughput...

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Bibliographic Details
Published in:Microbiology spectrum 2024-01, Vol.12 (1), p.e0289523-e0289523
Main Authors: Wang, Yu, Fu, Han, Shi, Xiao-Jie, Zhao, Guo-Ping, Lyu, Liang-Dong
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
antibiotic susceptibility
Antimicrobial Chemotherapy
drug resistance
Escherichia coli - genetics
Microbial Sensitivity Tests
Research Article
Rifampin - pharmacology
Rifamycins
Tn-Seq
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Summary:Rifamycins are a group of antibiotics with a wide antibacterial spectrum. Although the binding target of rifamycin has been well characterized, the mechanisms underlying the discrepant killing efficacy between gram-negative and gram-positive bacteria remain poorly understood. Using a high-throughput screen combined with targeted gene knockouts in the gram-negative model organism , we established that rifampicin efficacy is strongly dependent on several cellular pathways, including iron acquisition, DNA repair, aerobic respiration, and carbon metabolism. In addition, we provide evidence that these pathways modulate rifampicin efficacy in a manner distinct from redox-related killing. Our findings provide insights into the mechanism of rifamycin efficacy and may aid in the development of new antimicrobial adjuvants.
ISSN:2165-0497
2165-0497
DOI:10.1128/spectrum.02895-23