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.
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.
Authors: Wei Zhu; Yonghui Zhang; William Sinko; Mary E Hensler; Joshua Olson; Katie J Molohon; Steffen Lindert; Rong Cao; Kai Li; Ke Wang; Yang Wang; Yi-Liang Liu; Anna Sankovsky; César Augusto F de Oliveira; Douglas A Mitchell; Victor Nizet; J Andrew McCammon; Eric Oldfield Journal: Proc Natl Acad Sci U S A Date: 2012-12-17 Impact factor: 11.205