Anti-dormant mycobacterial activity and target analysis of nybomycin produced by a marine-derived Streptomyces sp.
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.
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan. Electronic address: araim@phs.osaka-u.ac.jp.
Masayoshi
M
Arai
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Kentaro
K
Kamiya
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Patamaporn
P
Pruksakorn
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Yuji
Y
Sumii
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Naoyuki
N
Kotoku
Nelson R. Mandela School of Medicine, University of KwaZulu Natal, 719 Umbilo Road, Congella, Durban 4013, South Africa.
Jean-Pierre
JP
Joubert
Nelson R. Mandela School of Medicine, University of KwaZulu Natal, 719 Umbilo Road, Congella, Durban 4013, South Africa.
Prashini
P
Moodley
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Chisu
C
Han
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan.
Dayoung
D
Shin
Graduate School of Pharmaceutical Sciences, Osaka University, Yamada-oka 1-6, Suita, Osaka 565-0871, Japan. Electronic address: kobayasi@phs.osaka-u.ac.jp.
Motomasa
M
Kobayashi
D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059001:Aquatic Organisms; D018929:Cell Culture Techniques; D003360:Cosmids / Q000737:chemistry / Q000378:metabolism; D004269:DNA, Bacterial / Q000037:antagonists & inhibitors* / Q000737:chemistry; D024881:Drug Resistance, Bacterial / Q000235:genetics; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009163:Mycobacterium bovis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D015363:Quinolones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013302:Streptomyces / Q000737:chemistry* / Q000378:metabolism
D000995:Antitubercular Agents; D004269:DNA, Bacterial; D015363:Quinolones; C005316:nybomycin
Antibiotic; Dormant; Nybomycin; Target identification; Tuberculosis