2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica |
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Authors: | Michaela K. Thielen Cody K. Vaneerd Dr. Manibarsha Goswami Prof. Dr. Erin E. Carlson Prof. Dr. John F. May |
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Affiliation: | 1. Department of Chemistry and Biochemistry, University of Wisconsin–La Crosse, 1725 State St, La Crosse, WI 54601 USA;2. Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455 USA |
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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 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. |
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Keywords: | Antibiotics histidine kinases polymyxin Salmonella enterica signal transduction |
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