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 Mg2+, 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.
Bibliographical noteFunding Information:
This research was supported by a Research Corporation for Science Advancement: Cottrell Teacher Scholar Ambassadors for PUI‐R1 Partnerships Award (J.F.M. and E.E.C.), by University of Wisconsin (UW) – La Crosse Undergraduate Research and Creativity Grants (M.K.T. and C.K.V.), by a UW – La Crosse College of Science and Health Dean's Distinguished Fellowship (M.K.T.), the National Institutes of Health (DP2OD008592 and R01GM134538‐01A1 to E.E.C.), an Alfred P. Sloan Fellowship (E.E.C.), and the University of Minnesota. We thank E. Groisman for providing strains of used in this study. Salmonella enterica
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- Salmonella enterica
- histidine kinases
- signal transduction
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't