Identification of a bacteria-produced benzisoxazole with antibiotic activity against multi-drug resistant *Acinetobacter baumannii*

The emergence of multi-drug resistant pathogenic bacteria represents a serious and growing threat to national healthcare systems. This paper reports a naturally occurring 1,2-benzisoxazole with potent antibiotic activity against clinical strains of multi-drug resistant *Acinetobacter baumannii*. The molecule, 3,6-dihydroxy-1,2-benzisoxazole (1), exhibits minimum inhibitory concentrations as low as 6.25 µg ml⁻¹ and is easily synthesized. In vitro testing suggests the natural compound is already optimized for activity. Supplementation of 4-hydroxybenzoate reversed the antibacterial effects, implicating chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyltransferase as potential targets.

Robert W. Deering, Kristen E. Whalen, Ivan Alvarez, Kathryn Daffinee, Maya Beganovic, Kerry L. LaPlante, Shreya Kishore, Sijing Zhao, Brent Cezairliyan, Shen Yu, Margaret Rosario, Tracy J. Mincer, David C. Rowley