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.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antitubercular Agents / chemistry
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Antitubercular Agents / isolation & purification
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Antitubercular Agents / pharmacology*
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Aquatic Organisms
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Cell Culture Techniques
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Cosmids / chemistry
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Cosmids / metabolism
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DNA, Bacterial / antagonists & inhibitors*
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DNA, Bacterial / chemistry
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Drug Resistance, Bacterial / genetics
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Microbial Sensitivity Tests
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Microbial Viability / drug effects
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Mycobacterium bovis / drug effects
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Mycobacterium bovis / genetics
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Mycobacterium bovis / metabolism
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Mycobacterium bovis / ultrastructure
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Mycobacterium smegmatis / drug effects
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Mycobacterium smegmatis / genetics
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Mycobacterium smegmatis / metabolism
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Mycobacterium smegmatis / ultrastructure
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Mycobacterium tuberculosis / drug effects*
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Mycobacterium tuberculosis / genetics
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Mycobacterium tuberculosis / metabolism
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Mycobacterium tuberculosis / ultrastructure
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Quinolones / chemistry
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Quinolones / isolation & purification
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Quinolones / pharmacology
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Streptomyces / chemistry*
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Streptomyces / metabolism
Substances
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Antitubercular Agents
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DNA, Bacterial
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Quinolones
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nybomycin