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2‐Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica
Author(s) -
Thielen Michaela K.,
Vaneerd Cody K.,
Goswami Manibarsha,
Carlson Erin E.,
May John F.
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000422
Subject(s) - salmonella enterica , polymyxin , salmonella , microbiology and biotechnology , virulence , innate immune system , biology , polymyxin b , antibiotic resistance , antibiotics , pathogenic bacteria , antimicrobial , histidine kinase , bacteria , immune system , virology , histidine , gene , immunology , biochemistry , genetics , enzyme
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 .