title: Mycobacterium Lysine ε-aminotransferase is a novel alarmone metabolism related persister gene via dysregulating the intracellular amino acid level.
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.
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, key laboratory of Eco-environment three gorges reservoir, Ministry of Education, School of Life Sciences, Southwest University. Chongqing 400715, China.
authors.forename: Xiangke
authors.initials: X
authors.lastname: Duan
authors.affiliation: Department of thoracic surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, key laboratory of Eco-environment three gorges reservoir, Ministry of Education, School of Life Sciences, Southwest University. Chongqing 400715, China.
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Du
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, key laboratory of Eco-environment three gorges reservoir, Ministry of Education, School of Life Sciences, Southwest University. Chongqing 400715, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, key laboratory of Eco-environment three gorges reservoir, Ministry of Education, School of Life Sciences, Southwest University. Chongqing 400715, China.|Hanhong College, Southwest University. Chongqing 400715, China.
authors.forename: Siyao
authors.initials: S
authors.lastname: Guo
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, key laboratory of Eco-environment three gorges reservoir, Ministry of Education, School of Life Sciences, Southwest University. Chongqing 400715, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, key laboratory of Eco-environment three gorges reservoir, Ministry of Education, School of Life Sciences, Southwest University. Chongqing 400715, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of thoracic surgery, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, key laboratory of Eco-environment three gorges reservoir, Ministry of Education, School of Life Sciences, Southwest University. Chongqing 400715, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Xie
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000995:Antitubercular Agents / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D023061:Gene Order; D056426:Genetic Loci; D042541:Intracellular Space; D051306:L-Lysine 6-Transaminase / Q000235:genetics* / Q000378:metabolism*; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics; D009154:Mutation; D009161:Mycobacterium / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000378:metabolism; D009643:Norfloxacin / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D000995:Antitubercular Agents; D051306:L-Lysine 6-Transaminase; D009643:Norfloxacin