Effect of n-octanesulphonylacetamide (OSA) on ATP and protein expression in Mycobacterium bovis BCG

The Journal of Antimicrobial Chemotherapy
N M ParrishJ D Dick

Abstract

To determine the effect on BCG of n-octanesulphonylacetamide (OSA), a novel compound of the class beta-sulphonylcarboxamides, which has potent in vitro activity against pathogenic mycobacteria. The effect of OSA in BCG was examined using two-dimensional protein electrophoresis. Treatment of BCG with OSA resulted in overexpression of two proteins identified as the b-subunit of ATP synthase (Rv1306) and a 17 kDa heat shock protein (Rv0251c). [35S]Methionine pulse-labelling revealed that overexpression occurred within as little as 3.5 h post-exposure. These results were confirmed by RT-PCR. ATP levels decreased in OSA-treated BCG at 5 min, and 1, 3 and 24 h, with a 64%, 45%, 54% and 73% reduction in ATP, respectively. Only dicyclohexylcarbodiimide (DCCD), a known ATP synthase inhibitor, had a similar effect. No appreciable difference in ATP level was observed in BCG treated with standard antimycobacterial drugs, additional respiratory chain inhibitors or a fatty acid synthase inhibitor at a comparable time-point. Protein synthesis decreased within 5 min of exposure to OSA (56%), DCCD (74%) and thenoyltrifluoroacetone (TTFA) (77%). Ethanol (2.3%) potentiated the activity of OSA. In contrast, no synergic effect was observed with str...Continue Reading

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Citations

Jul 12, 2011·American Journal of Therapeutics·Sujata Sharma, Mark A Yoder
May 15, 2012·European Journal of Medicinal Chemistry·M M ShulaevaV S Reznik
Aug 16, 2016·European Journal of Medicinal Chemistry·Jun-Jie KohShouping Liu
Mar 13, 2014·Antimicrobial Agents and Chemotherapy·Philippa A BlackBavesh D Kana
May 1, 2008·Expert Review of Vaccines·Lynn G DoverGurdyal S Besra
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Oct 29, 2008·The Journal of Biological Chemistry·William W MohnLindsay D Eltis
Feb 15, 2017·Frontiers in Microbiology·Amar M YewareDhiman Sarkar
Oct 30, 2020·Microbiology and Molecular Biology Reviews : MMBR·Alexander Cambré, Abram Aertsen
Feb 25, 2017·Microbiology Spectrum·Ben Gold, Carl Nathan
Feb 13, 2007·Bioorganic & Medicinal Chemistry·Yves L Janin

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