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

doi:10.1002/cbic.202000422

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 journal › Article › peer-review

4 Scopus citations

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 language	English (US)
Pages (from-to)	3500-3503
Number of pages	4
Journal	ChemBioChem
Volume	21
Issue number	24
DOIs	https://doi.org/10.1002/cbic.202000422
State	Published - Dec 11 2020
Externally published	Yes

Bibliographical note

Funding 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

Publisher Copyright:
© 2020 Wiley-VCH GmbH

Keywords

Antibiotics
Salmonella enterica
histidine kinases
polymyxin
signal transduction

Access

10.1002/cbic.202000422

OpenUrl availability

Full text

Cite this

@article{a064c7b345044a5cbb5493014976df1c,

title = "2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica",

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{\textquoteright}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.",

keywords = "Antibiotics, Salmonella enterica, histidine kinases, polymyxin, signal transduction",

author = "Thielen, {Michaela K.} and Vaneerd, {Cody K.} and Manibarsha Goswami and Carlson, {Erin E.} and May, {John F.}",

note = "Funding 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 Publisher Copyright: {\textcopyright} 2020 Wiley-VCH GmbH",

year = "2020",

month = dec,

day = "11",

doi = "10.1002/cbic.202000422",

language = "English (US)",

volume = "21",

pages = "3500--3503",

journal = "ChemBioChem",

issn = "1439-4227",

publisher = "Wiley-VCH Verlag",

number = "24",

}

TY - JOUR

T1 - 2-Aminobenzothiazoles Inhibit Virulence Gene Expression and Block Polymyxin Resistance in Salmonella enterica

AU - Thielen, Michaela K.

AU - Vaneerd, Cody K.

AU - Goswami, Manibarsha

AU - Carlson, Erin E.

AU - May, John F.

N1 - Funding 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 Publisher Copyright: © 2020 Wiley-VCH GmbH

PY - 2020/12/11

Y1 - 2020/12/11

N2 - 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.

AB - 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.

KW - Antibiotics

KW - Salmonella enterica

KW - histidine kinases

KW - polymyxin

KW - signal transduction

UR - http://www.scopus.com/inward/record.url?scp=85090596016&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85090596016&partnerID=8YFLogxK

U2 - 10.1002/cbic.202000422

DO - 10.1002/cbic.202000422

M3 - Article

C2 - 32750193

AN - SCOPUS:85090596016

SN - 1439-4227

VL - 21

SP - 3500

EP - 3503

JO - ChemBioChem

JF - ChemBioChem

IS - 24

ER -

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

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this