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Bioorg Med Chem Lett. 2011 Sep 15;21(18):5293-5. doi: 10.1016/j.bmcl.2011.07.029. Epub 2011 Jul 19.

The impact of fatty acids on the antibacterial properties of N-thiolated β-lactams.

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  • 1Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL, USA.

Abstract

Bacterial fatty acid synthesis (FAS) is a potentially important, albeit controversial, target for antimicrobial therapy. Recent studies have suggested that the addition of exogenous fatty acids (FAs) to growth media can circumvent the effects of FAS-targeting compounds on bacterial growth. Consequently, such agents may have limited in vivo applicability for the treatment of human disease, as free FAs are abundant within the body. Our group has previously developed N-thiolated β-lactams and found they function by interfering with FAS in select pathogenic bacteria, including MRSA. To determine if the FAS targeting activity of N-thiolated β-lactams can be abrogated by exogenous fatty acids, we performed MIC determinations for MRSA strains cultured with the fatty acids oleic acid and Tween 80. We find that, whilst the activity of the known FAS inhibitor triclosan is severely compromised by the addition of both oleic acid and Tween 80, exogenous FAs do not mitigate the antibacterial activity of N-thiolated β-lactams towards MRSA. Consequently, we propose that N-thiolated β-lactams are unique amongst FAS-inhibiting antimicrobials, as their effects are unimpeded by exogenous FAs.

Copyright © 2011 Elsevier Ltd. All rights reserved.

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