Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella

Ming Han Tsai, Sih Ru Wu, Hao Yuan Lee, Chyi Liang Chen, Tzou Yien Lin, Yhu Chering Huang, Cheng Hsun Chiu

研究成果: 雜誌貢獻文章

8 引文 (Scopus)

摘要

Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) is a global public health problem that complicates antimicrobial therapy. As an enteric pathogen, Salmonella must endure the presence of bile in the intestinal tract during the course of infection. In this study, we sought to identify Salmonella genes necessary for bile resistance and to investigate their association with antimicrobial resistance. Four genes related to bile resistance were identified, namely rfaP, rfbK, dam and tolC. The first three genes are involved in lipopolysaccharide synthesis, and tolC is associated with an efflux pump. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin B and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. Genetic analysis of 45 clinical isolates of NTS revealed that all isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration ≥0.125 mg/L) were associated with point mutations in the quinolone resistance-determining regions of the gyrA and parC genes. The efflux pump also played a role, as evidenced by the reduction in fluoroquinolone resistance when the TolC efflux pump was inhibited by Phe-Arg-β- naphthylamide, a competitive efflux pump inhibitor. Based on these results, we conclude that an intact membrane structure and the efflux pump system provide mechanisms enabling NTS to resist bile. Caution should be taken when using ciprofloxacin and polymyxin B to treat Salmonella enteric infection, as resistance to these agents involves the same mechanisms. Addition of an efflux pump inhibitor to fluoroquinolones may be an effective strategy to deal with the increasing resistance in NTS.
原文英語
頁(從 - 到)151-157
頁數7
期刊International Journal of Antimicrobial Agents
40
發行號2
DOIs
出版狀態已發佈 - 八月 2012
對外發佈Yes

指紋

Bile
Salmonella
Fluoroquinolones
Polymyxin B
Ciprofloxacin
Genes
Salmonella Infections
Quinolones
Microbial Sensitivity Tests
Point Mutation
Lipopolysaccharides
Public Health
Membranes
Infection

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

引用此文

Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella. / Tsai, Ming Han; Wu, Sih Ru; Lee, Hao Yuan; Chen, Chyi Liang; Lin, Tzou Yien; Huang, Yhu Chering; Chiu, Cheng Hsun.

於: International Journal of Antimicrobial Agents, 卷 40, 編號 2, 08.2012, p. 151-157.

研究成果: 雜誌貢獻文章

Tsai, Ming Han ; Wu, Sih Ru ; Lee, Hao Yuan ; Chen, Chyi Liang ; Lin, Tzou Yien ; Huang, Yhu Chering ; Chiu, Cheng Hsun. / Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella. 於: International Journal of Antimicrobial Agents. 2012 ; 卷 40, 編號 2. 頁 151-157.
@article{5fa521a5e9ea4aba89dfb8a4ff3554cf,
title = "Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella",
abstract = "Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) is a global public health problem that complicates antimicrobial therapy. As an enteric pathogen, Salmonella must endure the presence of bile in the intestinal tract during the course of infection. In this study, we sought to identify Salmonella genes necessary for bile resistance and to investigate their association with antimicrobial resistance. Four genes related to bile resistance were identified, namely rfaP, rfbK, dam and tolC. The first three genes are involved in lipopolysaccharide synthesis, and tolC is associated with an efflux pump. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin B and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. Genetic analysis of 45 clinical isolates of NTS revealed that all isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration ≥0.125 mg/L) were associated with point mutations in the quinolone resistance-determining regions of the gyrA and parC genes. The efflux pump also played a role, as evidenced by the reduction in fluoroquinolone resistance when the TolC efflux pump was inhibited by Phe-Arg-β- naphthylamide, a competitive efflux pump inhibitor. Based on these results, we conclude that an intact membrane structure and the efflux pump system provide mechanisms enabling NTS to resist bile. Caution should be taken when using ciprofloxacin and polymyxin B to treat Salmonella enteric infection, as resistance to these agents involves the same mechanisms. Addition of an efflux pump inhibitor to fluoroquinolones may be an effective strategy to deal with the increasing resistance in NTS.",
keywords = "Antimicrobial resistance, Bile susceptibility, Salmonella",
author = "Tsai, {Ming Han} and Wu, {Sih Ru} and Lee, {Hao Yuan} and Chen, {Chyi Liang} and Lin, {Tzou Yien} and Huang, {Yhu Chering} and Chiu, {Cheng Hsun}",
year = "2012",
month = "8",
doi = "10.1016/j.ijantimicag.2012.04.016",
language = "English",
volume = "40",
pages = "151--157",
journal = "International Journal of Antimicrobial Agents",
issn = "0924-8579",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Recognition of mechanisms involved in bile resistance important to halting antimicrobial resistance in nontyphoidal Salmonella

AU - Tsai, Ming Han

AU - Wu, Sih Ru

AU - Lee, Hao Yuan

AU - Chen, Chyi Liang

AU - Lin, Tzou Yien

AU - Huang, Yhu Chering

AU - Chiu, Cheng Hsun

PY - 2012/8

Y1 - 2012/8

N2 - Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) is a global public health problem that complicates antimicrobial therapy. As an enteric pathogen, Salmonella must endure the presence of bile in the intestinal tract during the course of infection. In this study, we sought to identify Salmonella genes necessary for bile resistance and to investigate their association with antimicrobial resistance. Four genes related to bile resistance were identified, namely rfaP, rfbK, dam and tolC. The first three genes are involved in lipopolysaccharide synthesis, and tolC is associated with an efflux pump. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin B and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. Genetic analysis of 45 clinical isolates of NTS revealed that all isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration ≥0.125 mg/L) were associated with point mutations in the quinolone resistance-determining regions of the gyrA and parC genes. The efflux pump also played a role, as evidenced by the reduction in fluoroquinolone resistance when the TolC efflux pump was inhibited by Phe-Arg-β- naphthylamide, a competitive efflux pump inhibitor. Based on these results, we conclude that an intact membrane structure and the efflux pump system provide mechanisms enabling NTS to resist bile. Caution should be taken when using ciprofloxacin and polymyxin B to treat Salmonella enteric infection, as resistance to these agents involves the same mechanisms. Addition of an efflux pump inhibitor to fluoroquinolones may be an effective strategy to deal with the increasing resistance in NTS.

AB - Increasing antimicrobial resistance in nontyphoidal Salmonella (NTS) is a global public health problem that complicates antimicrobial therapy. As an enteric pathogen, Salmonella must endure the presence of bile in the intestinal tract during the course of infection. In this study, we sought to identify Salmonella genes necessary for bile resistance and to investigate their association with antimicrobial resistance. Four genes related to bile resistance were identified, namely rfaP, rfbK, dam and tolC. The first three genes are involved in lipopolysaccharide synthesis, and tolC is associated with an efflux pump. Antimicrobial susceptibility testing showed increased susceptibility to polymyxin B and ciprofloxacin in rfaP and tolC mutants of Salmonella, respectively. Genetic analysis of 45 clinical isolates of NTS revealed that all isolates with reduced susceptibility to fluoroquinolones (minimum inhibitory concentration ≥0.125 mg/L) were associated with point mutations in the quinolone resistance-determining regions of the gyrA and parC genes. The efflux pump also played a role, as evidenced by the reduction in fluoroquinolone resistance when the TolC efflux pump was inhibited by Phe-Arg-β- naphthylamide, a competitive efflux pump inhibitor. Based on these results, we conclude that an intact membrane structure and the efflux pump system provide mechanisms enabling NTS to resist bile. Caution should be taken when using ciprofloxacin and polymyxin B to treat Salmonella enteric infection, as resistance to these agents involves the same mechanisms. Addition of an efflux pump inhibitor to fluoroquinolones may be an effective strategy to deal with the increasing resistance in NTS.

KW - Antimicrobial resistance

KW - Bile susceptibility

KW - Salmonella

UR - http://www.scopus.com/inward/record.url?scp=84864290433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864290433&partnerID=8YFLogxK

U2 - 10.1016/j.ijantimicag.2012.04.016

DO - 10.1016/j.ijantimicag.2012.04.016

M3 - Article

C2 - 22743016

AN - SCOPUS:84864290433

VL - 40

SP - 151

EP - 157

JO - International Journal of Antimicrobial Agents

JF - International Journal of Antimicrobial Agents

SN - 0924-8579

IS - 2

ER -