期刊
CHEMBIOCHEM
卷 21, 期 24, 页码 3500-3503出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202000422
关键词
Antibiotics; histidine kinases; polymyxin; Salmonella enterica; signal transduction
资金
- Research Corporation for Science Advancement: Cottrell Teacher Scholar Ambassadors for PUI-R1 Partnerships Award
- University of Wisconsin (UW) - La Crosse Undergraduate Research and Creativity Grants
- UW - La Crosse College of Science and Health Dean's Distinguished Fellowship
- National Institutes of Health [DP2OD008592, R01GM134538-01A1]
- Alfred P. Sloan Fellowship
- University of Minnesota
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 inSalmonella entericaserotype 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 genespagCandpagK. Furthermore, we discovered that 2-aminobenzothiazoles weakenSalmonella'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 bySalmonella.
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