Constitutive soxR mutations contribute to multiple-antibiotic resistance in clinical Escherichia coli isolates

Anastasia Koutsolioutsou, Samuel Peña-Llopis, Bruce Demple

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The soxRS regulon of Escherichia coli and Salmonella enterica is induced by redox-cycling compounds or nitric oxide and provides resistance to superoxide-generating agents, macrophage-generated nitric oxide, antibiotics, and organic solvents. We have previously shown that constitutive expression of soxRS can contribute to quinolone resistance in clinically relevant S. enterica. In this work, we have carried out an analysis of the mechanism of constitutive soxS expression and its role in antibiotic resistance in E. coli clinical isolates. We show that constitutive soxS expression in three out of six strains was caused by single point mutations in the soxR gene. The mutant SoxR proteins contributed to the multiple-antibiotic resistance phenotypes of the clinical strains and were sufficient to confer multiple-antibiotic resistance in a fresh genetic background. In the other three clinical isolates, we observed, for the first time, that elevated soxS expression was not due to mutations in soxR. The mechanism of such increased soxS expression remains unclear. The same E. coli clinical isolates harbored polymorphic soxR and soxS DNA sequences, also seen for the first time.

Original languageEnglish (US)
Pages (from-to)2746-2752
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume49
Issue number7
DOIs
StatePublished - Jul 2005

Fingerprint

Microbial Drug Resistance
Salmonella enterica
Escherichia coli
Mutation
Nitric Oxide
Regulon
Quinolones
Mutant Proteins
Point Mutation
Superoxides
Oxidation-Reduction
Macrophages
Anti-Bacterial Agents
Phenotype
Genes

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Constitutive soxR mutations contribute to multiple-antibiotic resistance in clinical Escherichia coli isolates. / Koutsolioutsou, Anastasia; Peña-Llopis, Samuel; Demple, Bruce.

In: Antimicrobial Agents and Chemotherapy, Vol. 49, No. 7, 07.2005, p. 2746-2752.

Research output: Contribution to journalArticle

Koutsolioutsou, Anastasia ; Peña-Llopis, Samuel ; Demple, Bruce. / Constitutive soxR mutations contribute to multiple-antibiotic resistance in clinical Escherichia coli isolates. In: Antimicrobial Agents and Chemotherapy. 2005 ; Vol. 49, No. 7. pp. 2746-2752.
@article{036c4ca8752544e2a1f854578cfc646f,
title = "Constitutive soxR mutations contribute to multiple-antibiotic resistance in clinical Escherichia coli isolates",
abstract = "The soxRS regulon of Escherichia coli and Salmonella enterica is induced by redox-cycling compounds or nitric oxide and provides resistance to superoxide-generating agents, macrophage-generated nitric oxide, antibiotics, and organic solvents. We have previously shown that constitutive expression of soxRS can contribute to quinolone resistance in clinically relevant S. enterica. In this work, we have carried out an analysis of the mechanism of constitutive soxS expression and its role in antibiotic resistance in E. coli clinical isolates. We show that constitutive soxS expression in three out of six strains was caused by single point mutations in the soxR gene. The mutant SoxR proteins contributed to the multiple-antibiotic resistance phenotypes of the clinical strains and were sufficient to confer multiple-antibiotic resistance in a fresh genetic background. In the other three clinical isolates, we observed, for the first time, that elevated soxS expression was not due to mutations in soxR. The mechanism of such increased soxS expression remains unclear. The same E. coli clinical isolates harbored polymorphic soxR and soxS DNA sequences, also seen for the first time.",
author = "Anastasia Koutsolioutsou and Samuel Pe{\~n}a-Llopis and Bruce Demple",
year = "2005",
month = "7",
doi = "10.1128/AAC.49.7.2746-2752.2005",
language = "English (US)",
volume = "49",
pages = "2746--2752",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "7",

}

TY - JOUR

T1 - Constitutive soxR mutations contribute to multiple-antibiotic resistance in clinical Escherichia coli isolates

AU - Koutsolioutsou, Anastasia

AU - Peña-Llopis, Samuel

AU - Demple, Bruce

PY - 2005/7

Y1 - 2005/7

N2 - The soxRS regulon of Escherichia coli and Salmonella enterica is induced by redox-cycling compounds or nitric oxide and provides resistance to superoxide-generating agents, macrophage-generated nitric oxide, antibiotics, and organic solvents. We have previously shown that constitutive expression of soxRS can contribute to quinolone resistance in clinically relevant S. enterica. In this work, we have carried out an analysis of the mechanism of constitutive soxS expression and its role in antibiotic resistance in E. coli clinical isolates. We show that constitutive soxS expression in three out of six strains was caused by single point mutations in the soxR gene. The mutant SoxR proteins contributed to the multiple-antibiotic resistance phenotypes of the clinical strains and were sufficient to confer multiple-antibiotic resistance in a fresh genetic background. In the other three clinical isolates, we observed, for the first time, that elevated soxS expression was not due to mutations in soxR. The mechanism of such increased soxS expression remains unclear. The same E. coli clinical isolates harbored polymorphic soxR and soxS DNA sequences, also seen for the first time.

AB - The soxRS regulon of Escherichia coli and Salmonella enterica is induced by redox-cycling compounds or nitric oxide and provides resistance to superoxide-generating agents, macrophage-generated nitric oxide, antibiotics, and organic solvents. We have previously shown that constitutive expression of soxRS can contribute to quinolone resistance in clinically relevant S. enterica. In this work, we have carried out an analysis of the mechanism of constitutive soxS expression and its role in antibiotic resistance in E. coli clinical isolates. We show that constitutive soxS expression in three out of six strains was caused by single point mutations in the soxR gene. The mutant SoxR proteins contributed to the multiple-antibiotic resistance phenotypes of the clinical strains and were sufficient to confer multiple-antibiotic resistance in a fresh genetic background. In the other three clinical isolates, we observed, for the first time, that elevated soxS expression was not due to mutations in soxR. The mechanism of such increased soxS expression remains unclear. The same E. coli clinical isolates harbored polymorphic soxR and soxS DNA sequences, also seen for the first time.

UR - http://www.scopus.com/inward/record.url?scp=21444435491&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21444435491&partnerID=8YFLogxK

U2 - 10.1128/AAC.49.7.2746-2752.2005

DO - 10.1128/AAC.49.7.2746-2752.2005

M3 - Article

C2 - 15980345

AN - SCOPUS:21444435491

VL - 49

SP - 2746

EP - 2752

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 7

ER -