2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica

Michaela K. Thielen, Cody K. Vaneerd, Manibarsha Goswami, Erin E. Carlson, John F. May

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalChemBioChem
DOIs
StateAccepted/In press - 2020

Keywords

  • Antibiotics
  • Salmonella enterica
  • histidine kinases
  • polymyxin
  • signal transduction

PubMed: MeSH publication types

  • Journal Article

Fingerprint Dive into the research topics of '2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica'. Together they form a unique fingerprint.

  • Cite this