Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp

  • Bioorg Med Chem. 2015 Jul 1;23(13):3534-41. doi: 10.1016/j.bmc.2015.04.033.
Masayoshi Arai  1 ,  Kentaro Kamiya  2 ,  Patamaporn Pruksakorn  2 ,  Yuji Sumii  2 ,  Naoyuki Kotoku  2 ,  Jean-Pierre Joubert  3 ,  Prashini Moodley  3 ,  Chisu Han  2 ,  Dayoung Shin  2 ,  Motomasa Kobayashi  4
Affiliations
  • 1. Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan. Electronic address: [email protected].
  • 2. Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
  • 3. Nelson R. Mandela School of Medicine, University of KwaZulu Natal, 719 Umbilo Road, Congella, Durban 4013, South Africa.
  • 4. Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan. Electronic address: [email protected].
PMID: 25934225 DOI: 10.1016/j.bmc.2015.04.033
Abstract

In the course of our search for anti-dormant Mycobacterial substances, nybomycin (1) was re-discovered from the culture broth of a marine-derived Streptomyces sp. on the bioassay-guided separation. Compound 1 showed anti-microbial activity against Mycobacterium smegmatis and Mycobacterium bovis BCG with the MIC of 1.0μg/mL under both actively growing aerobic conditions and dormancy inducing hypoxic conditions. Compound 1 is also effective to Mycobacterium tuberculosis including the clinically isolated strains. The mechanistic analysis indicated that 1 bound to DNA and induces a unique morphological change to mycobacterial bacilli leading the Bacterial cell death.

Keywords
Antibiotic; Dormant; Nybomycin; Target identification; Tuberculosis.
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