title: Branched-chain amino acid supplementation promotes aerobic growth of Salmonella Typhimurium under nitrosative stress conditions.
abstract: Nitric oxide (NO) inactivates iron-sulfur enzymes in bacterial amino acid biosynthetic pathways, causing amino acid auxotrophy. We demonstrate that exogenous supplementation with branched-chain amino acids (BCAA) can restore the NO resistance of hmp mutant Salmonella Typhimurium lacking principal NO-metabolizing enzyme flavohemoglobin, and of mutants further lacking iron-sulfur enzymes dihydroxy-acid dehydratase (IlvD) and isopropylmalate isomerase (LeuCD) that are essential for BCAA biosynthesis, in an oxygen-dependent manner. BCAA supplementation did not affect the NO consumption rate of S. Typhimurium, suggesting the BCAA-promoted NO resistance independent of NO metabolism. BCAA supplementation also induced intracellular survival of ilvD and leuCD mutants at wild-type levels inside RAW 264.7 macrophages that produce constant amounts of NO regardless of varied supplemental BCAA concentrations. Our results suggest that the NO-induced BCAA auxotrophy of Salmonella, due to inactivation of iron-sulfur enzymes for BCAA biosynthesis, could be rescued by bacterial taking up exogenous BCAA available in oxic environments.
authors.affiliation: Department of Microbiology and Immunology, Chosun University School of Dentistry, Gwangju, 501-759, Republic of Korea.
authors.forename: Yoon Mee
authors.initials: YM
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, Chosun University School of Dentistry, Gwangju, 501-759, Republic of Korea.
authors.forename: Hwa Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju, 501-746, Republic of Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Oral Biochemistry, Chosun University School of Dentistry, Gwangju, 501-759, Republic of Korea.
authors.forename: Joong-Ki
authors.initials: JK
authors.lastname: Kook
authors.affiliation: Department of Microbiology, Chonnam National University Medical School, Gwangju, 501-746, Republic of Korea.
authors.forename: Hyon E
authors.initials: HE
authors.lastname: Choy
authors.affiliation: College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Hahn
authors.affiliation: Department of Microbiology and Immunology, Chosun University School of Dentistry, Gwangju, 501-759, Republic of Korea. isbang@chosun.ac.kr.
authors.forename: Iel Soo
authors.initials: IS
authors.lastname: Bang
mesh_terms: D000332:Aerobiosis; D000596:Amino Acids / Q000378:metabolism; D000597:Amino Acids, Branched-Chain / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D002460:Cell Line; D006420:Hemeproteins / Q000235:genetics; D006836:Hydro-Lyases / Q000235:genetics; D007501:Iron / Q000378:metabolism; D007535:Isomerases / Q000235:genetics; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D013312:Stress, Physiological
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D001426:Bacterial Proteins; D006420:Hemeproteins; C086193:flavohemoprotein, Bacteria; D009569:Nitric Oxide; D007501:Iron; D006836:Hydro-Lyases; C032241:isopropylmalate isomerase; C020052:dihydroxyacid dehydratase; D007535:Isomerases
keywords: Branched-chain amino acids; Iron-sulfur cluster enzyme; Nitric oxide; Salmonella Typhimurium