Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens

Sophie Brinster, Gilles Lamberet, Bart Staels, Patrick Trieu-Cuot, Alexandra Gruss () and Claire Poyart ()
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Sophie Brinster: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France
Gilles Lamberet: INRA, UR888, Unité Bactéries Lactiques et Pathogènes Opportunistes, F-78350, Jouy en Josas, France
Bart Staels: Institut Pasteur de Lille, INSERM UMR545, Université Lille 2
Patrick Trieu-Cuot: Institut Pasteur, Unité de Biologie des Bactéries Pathogènes à Gram Positif, URA CNRS 2172, Paris, France
Alexandra Gruss: INRA, UR888, Unité Bactéries Lactiques et Pathogènes Opportunistes, F-78350, Jouy en Josas, France
Claire Poyart: Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France

Nature, 2009, vol. 458, issue 7234, 83-86

Abstract: Antibiotic target missed? The type II fatty acid synthesis (FASII) pathway has been suggested to be a promising antimicrobial target, and the antibiotics platensimycin and platencin that target this pathway are claimed to be potentially effective against multiresistant Gram-positive bacteria. But a new study casts doubt on the value of this approach. Clinical isolates of a series of Gram-positive pathogens, including staphylococci, streptococci, pneumococci, and enterococci, are shown to overcome drug-induced blockade of FASII pathway inhibition when supplied with exogenous fatty acids either in laboratory growth medium or when infecting animals. Importantly, human serum is a highly effective source of fatty acids.

Date: 2009
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DOI: 10.1038/nature07772

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