Reactive Oxygen Detoxification Contributes to Mycobacterium abscessus Antibiotic Survival.

Autor:	Bates NA; Department of Internal Medicine, University of California, Davis, California, USA.; Graduate Group in Immunology, University of California, Davis, California, USA., Rodriguez R; Department of Molecular & Cell Biology, University of California, Berkeley, California, USA.; Department of Plant & Microbial Biology, University of California, Berkeley, California, USA., Drwich R; Department of Internal Medicine, University of California, Davis, California, USA., Ray A; Microbiology Graduate Group, University of California, Davis, California, USA., Stanley SA; Department of Molecular & Cell Biology, University of California, Berkeley, California, USA., Penn BH; Department of Internal Medicine, University of California, Davis, California, USA.; Department of Medical Microbiology and Immunology, University of California, Davis, California, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Oct 29. Date of Electronic Publication: 2024 Oct 29.
DOI:	10.1101/2024.10.13.618103
Abstrakt:	When a population of bacteria encounter a bactericidal antibiotic most cells die rapidly. However, a sub-population, known as "persister cells", can survive for prolonged periods in a non-growing, but viable, state. Persister cell frequency is dramatically increased by stresses such as nutrient deprivation, but it is unclear what pathways are required to maintain viability, and how this process is regulated. To identify the genetic determinants of antibiotic persistence in mycobacteria, we carried out transposon mutagenesis high-throughput sequencing (Tn-Seq) screens in Mycobacterium abscessus ( Mabs ). This analysis identified genes essential in both spontaneous and stress-induced persister cells, allowing the first genetic comparison of these states in mycobacteria, and unexpectedly identified multiple genes involved in the detoxification of reactive oxygen species (ROS). We found that endogenous ROS were generated following antibiotic exposure, and that the KatG catalase-peroxidase contributed to survival in both spontaneous and starvation-induced persisters. We also found that that hypoxia significantly impaired bacterial killing, and notably, in the absence of oxygen, KatG became dispensable. Thus, the lethality of some antibiotics is amplified by toxic ROS accumulation, and persister cells depend on detoxification systems to remain viable. Competing Interests: CONFLICTS OF INTEREST BHP and SAS serve on the scientific advisory board of X-Biotics Therapeutics.
Databáze:	MEDLINE
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