biostudies-literatureLee HJKorea Evaluation Institute of Industrial TechnologyNational Research Foundation of Korea683https://www.ebi.ac.uk/biostudies/studies/S-EPMC9137938biostudies-literatureUnknown11(5)Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a pathogenic bacterium that causes severe diseases in humans. For decades, MRSA has acquired substantial resistance against conventional antibiotics through regulatory adaptation, thereby posing a challenge for treating MRSA infection. One of the emerging strategies to combat MRSA is the combinatory use of antibacterial agents. Based on the dramatic change in phospholipid fatty acid (PLFA) composition of MRSA in previous results, this study investigated branched-chain amino acid derivatives (precursors of fatty acid synthesis of cell membrane) and discovered the antimicrobial potency of D-norvaline. The compound, which can act synergistically with oxacillin, is among the three leucine-tRNA synthetase inhibitors with high potency Antibiotics (Basel, Switzerland)Leucyl-tRNA Synthetase Inhibitor, D-Norvaline, in Combination with Oxacillin, Is Effective against Methicillin-Resistant <i>Staphylococcus aureus</i>.PMC9137938NRF-2022R1A2C200313820016324NRF-2019M3E6A11039792017M3A9E4077234Kim SYang YHKim BKim WJoo HSJung HLee SHKim YGLee HJCho DHKim JSfalseLeucyl-tRNA Synthetase Inhibitor, D-Norvaline, in Combination with Oxacillin, Is Effective against Methicillin-Resistant <i>Staphylococcus aureus</i>.Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is a pathogenic bacterium that causes severe diseases in humans. For decades, MRSA has acquired substantial resistance against conventional antibiotics through regulatory adaptation, thereby posing a challenge for treating MRSA infection. One of the emerging strategies to combat MRSA is the combinatory use of antibacterial agents. Based on the dramatic change in phospholipid fatty acid (PLFA) composition of MRSA in previous results, this study investigated branched-chain amino acid derivatives (precursors of fatty acid synthesis of cell membrane) and discovered the antimicrobial potency of D-norvaline. The compound, which can act synergistically with oxacillin, is among the three leucine-tRNA synthetase inhibitors with high potency 2022-01-01T00:00:00Z2022 May2025-04-04T22:15:27.101Z2025-04-04T22:15:27.101ZS-EPMC91379383562532710.3390/antibiotics11050683