Resistance mapping and mode of action of a novel class of antibacterial anthranilic acids: evidence for disruption of cell wall biosynthesis.
OBJECTIVE
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.
Infectious Diseases Biology, Pharmacia Corporation, 301 Henrietta Street, Kalamazoo, MI 49007, USA.
John E
JE
Mott
Bailin A
BA
Shaw
James F
JF
Smith
Paul D
PD
Bonin
Donna L
DL
Romero
Keith R
KR
Marotti
Alita A
AA
Miller
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002473:Cell Wall / Q000187:drug effects*; D004252:DNA Mutational Analysis; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D020043:Genes, Essential; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*; D014161:Transduction, Genetic; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D062367:ortho-Aminobenzoates