2. Academic Validation
  3. Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus

Activity of LCB01-0371, a Novel Oxazolidinone, against Mycobacterium abscessus

  • Antimicrob Agents Chemother. 2017 Aug 24;61(9):e02752-16. doi: 10.1128/AAC.02752-16.
Tae Sung Kim 1 2,  Jin Ho Choe 1 2,  Young Jae Kim 1,  Chul-Su Yang 3,  Hyun-Jin Kwon 4,  Jinsun Jeong 5,  Guehye Kim 5,  Da Eun Park 5,  Eun-Kyeong Jo 1 2,  Young-Lag Cho 4,  Jichan Jang 6 7
Affiliations

Affiliations

  • 1 Department of Microbiology, Chungnam National University School of Medicine, Daejeon, South Korea.
  • 2 Department of Medical Science, Chungnam National University School of Medicine, Daejeon, South Korea.
  • 3 Department of Molecular and Life Science, Hanyang University, Ansan, South Korea.
  • 4 LegoChem Biosciences, Inc., Daejeon, South Korea.
  • 5 Division of Applied Life Science (BK21plus Program), Gyeongsang National University, Jinju, South Korea.
  • 6 Division of Applied Life Science (BK21plus Program), Gyeongsang National University, Jinju, South Korea [email protected].
  • 7 Division of Life Science, Research Institute of Life Sciences, Gyeongsang National University, Jinju, South Korea.
PMID: 28674049 DOI: 10.1128/AAC.02752-16
Abstract

Mycobacterium abscessus is a highly pathogenic drug-resistant rapidly growing mycobacterium. In this study, we evaluated the in vitro, intracellular, and in vivo activities of LCB01-0371, a novel and safe Oxazolidinone derivative, for the treatment of M. abscessus Infection and compared its resistance to that of other Oxazolidinone drugs. LCB01-0371 was effective against several M. abscessus strains in vitro and in a macrophage model of Infection. In the murine model, a similar efficacy to linezolid was achieved, especially in the lungs. We induced laboratory-generated resistance to LCB01-0371; sequencing analysis revealed mutations in rplC of T424C and G419A and a nucleotide insertion at the 503 position. Furthermore, LCB01-0371 inhibited the growth of amikacin-, cefoxitin-, and clarithromycin-resistant strains. Collectively, our data indicate that LCB01-0371 might represent a promising new class of oxazolidinones with improved safety, which may replace linezolid for the treatment of M. abscessus.

Keywords

LCB01-0371; Mycobacterium abscessus; drug resistance; oxazolidinone.

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