Resistance mapping and mode of action of a novel class of antibacterial anthranilic acids: evidence for disruption of cell wall biosynthesis.
作者信息
Mott John E, Shaw Bailin A, Smith James F, Bonin Paul D, Romero Donna L, Marotti Keith R, Miller Alita A
机构信息
Infectious Diseases Biology, Pharmacia Corporation, 301 Henrietta Street, Kalamazoo, MI 49007, USA.
出版信息
J Antimicrob Chemother. 2008 Oct;62(4):720-9. doi: 10.1093/jac/dkn261. Epub 2008 Jun 19.
OBJECTIVES
The aim of this study was to characterize the mechanism of action of a novel class of bacterial protein synthesis inhibitors identified in a high-throughput coupled transcription-translation assay.
METHODS
Evaluation of the cross-resistance to antibiotics with known mechanisms of action, resistance mapping and biochemical characterization of a novel class of antibacterial anthranilic acids was performed.
RESULTS
No cross-resistance to established classes of antibiotics was found. Resistance was mapped to SA1575, an essential, integral membrane protein predicted to be involved in polysaccharide biosynthesis. Biochemical analysis demonstrated the inhibition of cell wall biosynthesis.
CONCLUSIONS
This novel class of antibacterial anthranilic acids inhibits cell wall biosynthesis. Resistance mapped to SA1575, which may represent a novel target for antibacterial drug discovery.
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