Mycobacterium Lysine ε-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level

Scientific Reports
Xiangke DuanJianping Xie

Abstract

Bacterial persisters, usually slow-growing, non-replicating cells highly tolerant to antibiotics, play a crucial role contributing to the recalcitrance of chronic infections and treatment failure. Understanding the molecular mechanism of persister cells formation and maintenance would obviously inspire the discovery of new antibiotics. The significant upregulation of Mycobacterium tuberculosis Rv3290c, a highly conserved mycobacterial lysine ε-aminotransferase (LAT) during hypoxia persistent model, suggested a role of LAT in persistence. To test this, a lat deleted Mycobacterium smegmatis was constructed. The expression of transcriptional regulator leucine-responsive regulatory protein (LrpA) and the amino acids abundance in M. smegmatis lat deletion mutants were lowered. Thus, the persistence capacity of the deletion mutant was impaired upon norfloxacin exposure under nutrient starvation. In summary, our study firstly reported the involvement of mycobacterium LAT in persister formation, and possibly through altering the intracellular amino acid metabolism balance.

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Citations

Sep 19, 2019·Nature Communications·Erik J HasenoehrlMichael Berney
Jun 28, 2018·Applied Microbiology and Biotechnology·Xiaoyu WangJianping Xie
Jun 27, 2019·Mini Reviews in Medicinal Chemistry·Gopichand GuttiSushil Kumar Singh
Nov 27, 2020·International Journal of Molecular Sciences·André CampaniçoFrancisca Lopes

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Methods Mentioned

BETA
PCR
reverse transcription-PCR

Software Mentioned

BLAST

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