2‐Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica. (11th September 2020)

• Record Type: Journal Article
• Authors: Thielen, Michaela K.; Vaneerd, Cody K.; Goswami, Manibarsha; Carlson, Erin E.; May, John F.
• Is Part Of: Chembiochem. Volume 21:Number 24(2020)
• Page Start: 3500
• Page End: 3503
• Publication Date: 2020-09-11
• Subjects: Antibiotics -- histidine kinases -- polymyxin -- Salmonella enterica -- signal transduction; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202000422
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: 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 (HKs) to resist innate immune defenses such as cationic antimicrobial peptides (CAMPs). Herein, we report that 2‐aminobenzothiazoles block histidine kinase‐dependent phenotypes in Salmonella enterica serotype Typhimurium. We found that 2‐aminobenzothiazoles inhibited growth under 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 . Abstract : For the defense : Salmonella enterica must fight antibacterial conditions encountered during an infection in order to cause food‐borne illness or typhoid fever. We discovered a class of small molecules, 2‐aminobenzothiazoles, that inhibit the expression of certain virulence genes and weaken Salmonella 's resistance to polymyxin antimicrobial peptides. The findings suggest that these compounds can block Salmonella resistance to host immune defenses.