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Limited Multidrug Resistance Efflux Pump Overexpression among Multidrug-Resistant Escherichia coli Strains of ST131
- Source :
- Antimicrobial Agents and Chemotherapy, 65(4):ARTN e01735-20. AMER SOC MICROBIOLOGY, Antimicrob Agents Chemother
- Publication Year :
- 2021
- Publisher :
- American Society for Microbiology, 2021.
-
Abstract
- Gram-negative bacteria partly rely on efflux pumps to facilitate growth under stressful conditions and to increase resistance to a wide variety of commonly used drugs. In recent years, Escherichia coli sequence type 131 (ST131) has emerged as a major cause of extraintestinal infection frequently exhibiting a multidrug resistance (MDR) phenotype. The contribution of efflux to MDR in emerging E. coli MDR clones, however, is not well studied. We characterized strains from an international collection of clinical MDR E. coli isolates by MIC testing with and without the addition of the AcrAB-TolC efflux inhibitor 1-(1-naphthylmethyl)-piperazine (NMP). MIC data for 6 antimicrobial agents and their reversion by NMP were analyzed by principal-component analysis (PCA). PCA revealed a group of 17 MDR E. coli isolates (n = 34) exhibiting increased susceptibility to treatment with NMP, suggesting an enhanced contribution of efflux pumps to antimicrobial resistance in these strains (termed enhanced efflux phenotype [EEP] strains). Only 1/17 EEP strains versus 12/17 non-EEP MDR strains belonged to the ST131 clonal group. Whole-genome sequencing revealed marked differences in efflux-related genes between EEP and control strains, with the majority of notable amino acid substitutions occurring in AcrR, MarR, and SoxR. Quantitative reverse transcription-PCR (qRT-PCR) of multiple efflux-related genes showed significant overexpression of the AcrAB-TolC system in EEP strains, whereas in the remaining strains, we found enhanced expression of alternative efflux proteins. We conclude that a proportion of MDR E. coli strains exhibit an EEP, which is linked to an overexpression of the AcrAB-TolC efflux pump and a distinct array of genomic variations. Members of ST131, although highly successful, are less likely to exhibit the EEP.
- Subjects :
- EXPRESSION
ST131
Reversion
Microbial Sensitivity Tests
SUSCEPTIBILITY
Biology
medicine.disease_cause
MECHANISMS
Microbiology
03 medical and health sciences
Antibiotic resistance
Mechanisms of Resistance
Drug Resistance, Multiple, Bacterial
Escherichia coli
medicine
Pharmacology (medical)
ACRR
FLUOROQUINOLONE RESISTANCE
Gene
efflux pump inhibitors
030304 developmental biology
Pharmacology
0303 health sciences
IDENTIFICATION
MUTATIONS
030306 microbiology
Escherichia coli Proteins
E. coli
ANTIBIOTIC-RESISTANCE
AcrB
biology.organism_classification
Antimicrobial
efflux
Anti-Bacterial Agents
Multiple drug resistance
Infectious Diseases
MUTANTS
Efflux
Bacteria
GENETIC-CHARACTERIZATION
Subjects
Details
- ISSN :
- 10986596 and 00664804
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Antimicrobial Agents and Chemotherapy
- Accession number :
- edsair.doi.dedup.....e2d4b0091856e66d4dea04fc07fdf28e