2-Aminobenzothiazoles inhibit virulence gene expression and block polymyxin resistance in Salmonella enterica.

One promising strategy to combat antibiotic-resistant bacteria is to develop compounds that block bacterial defenses against antibacterial conditions produced by the innate immune system. Salmonella enterica , which causes food-borne gastroenteritis and typhoid fever, requires histidine kinases to resist innate immune defenses such as cationic antimicrobial peptides (CAMPs). Here, we report that 2-aminobenzothiazoles block histidine kinase-dependent phenotypes in Salmonella enterica serotype Typhimurium. We found that 2-aminobenzothiazoles inhibited growth in low Mg 2+ , a stressful condition that requires histidine kinase-mediated responses, and decreased expression of the virulence genes pagC and pagK . Furthermore, we discovered that 2-aminobenzothiazoles weaken Salmonella 's resistance to polymyxin B and polymyxin E, which are last-line antibiotics and models for host defense CAMPs. These findings raise the possibilities that 2-aminobenzothiazoles can block HK-mediated bacterial defenses and can be used in combination with polymyxins to treat infections caused by Salmonella .