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Article

Leucyl-tRNA Synthetase Inhibitor, D-Norvaline, in Combination with Oxacillin, Is Effective against Methicillin-Resistant Staphylococcus aureus

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Department of Biological Engineering, College of Engineering, Konkuk University, Seoul 05029, Korea
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College of Pharmacy and Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea
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Department of Chemical Engineering, Soongsil University, Seoul 06978, Korea
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Department of Laboratory Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul 05355, Korea
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Department of Biotechnology, College of Engineering, Duksung Women’s University, Seoul 01369, Korea
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Department of Pharmacy, College of Pharmacy, Jeju National University, Jeju-si 63243, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Francois Vandenesch
Antibiotics 2022, 11(5), 683; https://doi.org/10.3390/antibiotics11050683
Received: 11 April 2022 / Revised: 11 May 2022 / Accepted: 16 May 2022 / Published: 18 May 2022
Methicillin-resistant Staphylococcus aureus (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 to inhibit MRSA cell growth and biofilm formation. PLFA analysis and membrane properties revealed that D-norvaline decreased the overall amount of PLFA, increasing the fluidity and decreasing the hydrophobicity of the bacterial cell membrane. Additionally, we observed genetic differences to explore the response to D-norvaline. Furthermore, deletion mutants and clinically isolated MRSA strains were treated with D-norvaline. The study revealed that D-norvaline, with low concentrations of oxacillin, was effective in killing several MRSA strains. In summary, our findings provide a new combination of aminoacyl-tRNA synthetase inhibitor D-norvaline and oxacillin, which is effective against MRSA. View Full-Text
Keywords: MRSA; D-norvaline; aminoacyl-tRNA synthetase inhibitor; drug combination therapy MRSA; D-norvaline; aminoacyl-tRNA synthetase inhibitor; drug combination therapy
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MDPI and ACS Style

Lee, H.-J.; Kim, B.; Kim, S.; Cho, D.-H.; Jung, H.; Kim, W.; Kim, Y.-G.; Kim, J.-S.; Joo, H.-S.; Lee, S.-H.; Yang, Y.-H. Leucyl-tRNA Synthetase Inhibitor, D-Norvaline, in Combination with Oxacillin, Is Effective against Methicillin-Resistant Staphylococcus aureus. Antibiotics 2022, 11, 683. https://doi.org/10.3390/antibiotics11050683

AMA Style

Lee H-J, Kim B, Kim S, Cho D-H, Jung H, Kim W, Kim Y-G, Kim J-S, Joo H-S, Lee S-H, Yang Y-H. Leucyl-tRNA Synthetase Inhibitor, D-Norvaline, in Combination with Oxacillin, Is Effective against Methicillin-Resistant Staphylococcus aureus. Antibiotics. 2022; 11(5):683. https://doi.org/10.3390/antibiotics11050683

Chicago/Turabian Style

Lee, Hong-Ju, Byungchan Kim, Suhyun Kim, Do-Hyun Cho, Heeju Jung, Wooseong Kim, Yun-Gon Kim, Jae-Seok Kim, Hwang-Soo Joo, Sang-Ho Lee, and Yung-Hun Yang. 2022. "Leucyl-tRNA Synthetase Inhibitor, D-Norvaline, in Combination with Oxacillin, Is Effective against Methicillin-Resistant Staphylococcus aureus" Antibiotics 11, no. 5: 683. https://doi.org/10.3390/antibiotics11050683

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