Activity of DSA against anaerobically adapted Mycobacterium bovis BCG in vitro

Summary DSA is a β-sulfonylacetamide with in vitro activity against pathogenic mycobacteria. Although the enzymatic target(s) of DSA has not been identified, studies to date suggest that this class of compounds may interfere directly or indirectly with ATP synthase and other components of the mycoba...

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Bibliographic Details
Published in:Tuberculosis (Edinburgh, Scotland) Scotland), 2009-07, Vol.89 (4), p.325-327
Main Authors: Parrish, Nicole M, Ko, Chiew G, Dick, James D
Format: Article
Language:English
Subjects:
Adaptation, Physiological
Anaerobiosis
Antitubercular Agents - pharmacology
ATP synthase
Infectious Disease
Latency
Mycobacterium bovis
Mycobacterium bovis - drug effects
Mycobacterium bovis - growth & development
Mycobacterium tuberculosis
n-decanesulfonylacetamide
Pulmonary/Respiratory
Rifampin-tolerant persisters
Sulfonamides - pharmacology
Wayne model
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Summary:Summary DSA is a β-sulfonylacetamide with in vitro activity against pathogenic mycobacteria. Although the enzymatic target(s) of DSA has not been identified, studies to date suggest that this class of compounds may interfere directly or indirectly with ATP synthase and other components of the mycobacterial respiratory chain. In this study we further evaluated the in vitro activity of DSA against anaerobically adapted BCG using two established models. DSA killed BCG in the anaerobic Wayne model. Bactericidal activity ranged from >99% to 60%. DSA killed rifampin-tolerant persisters with a reduction in viable counts of 1.5 log10 versus controls. Conclusive identification of the DSA-specific target(s) will permit a better understanding of the unique mechanism of action of this class of compounds against both aerobically growing and anaerobically adapted bacilli in vitro.
ISSN:1472-9792
1873-281X
DOI:10.1016/j.tube.2009.05.002