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J Antimicrob Chemother. 2008 Oct;62(4):720-9. doi: 10.1093/jac/dkn261. Epub 2008 Jun 19.

Resistance mapping and mode of action of a novel class of antibacterial anthranilic acids: evidence for disruption of cell wall biosynthesis.

Author information

1
Infectious Diseases Biology, Pharmacia Corporation, 301 Henrietta Street, Kalamazoo, MI 49007, USA.

Abstract

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.

PMID:
18567575
DOI:
10.1093/jac/dkn261
[Indexed for MEDLINE]

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