Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp.
Arai M, Kamiya K, Pruksakorn P, Sumii Y, Kotoku N, Joubert JP, Moodley P, Han C, Shin D, Kobayashi M.
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.