Format

Send to

Choose Destination
J Antimicrob Chemother. 2015 Sep;70(9):2524-7. doi: 10.1093/jac/dkv144. Epub 2015 Jun 3.

Effect of the efflux pump QepA2 combined with chromosomally mediated mechanisms on quinolone resistance and bacterial fitness in Escherichia coli.

Author information

1
Unidad de Enfermedades Infecciosas y Microbiología Clínica, Hospital Universitario Virgen Macarena, Sevilla, Spain jesmacbar@hotmail.com.
2
Departamento de Microbiología, Universidad de Sevilla, Sevilla, Spain Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain.
3
Departamento de Microbiología, Universidad de Sevilla, Sevilla, Spain.
4
Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain Hospital Universitario Marques de Valdecilla and Valdecilla Biomedical Research Institute (IDIVAL), Santander, Spain Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain.
5
Unidad de Enfermedades Infecciosas y Microbiología Clínica, Hospital Universitario Virgen Macarena, Sevilla, Spain Departamento de Microbiología, Universidad de Sevilla, Sevilla, Spain Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain.

Abstract

OBJECTIVES:

The aim of the study was to determine the interplay between the plasmid-mediated qepA2 gene and multiple chromosomally mediated fluoroquinolone resistance determinants in the development of fluoroquinolone resistance in Escherichia coli and its influence on bacterial fitness.

METHODS:

E. coli ATCC 25922 and derived isogenic strains harbouring different chromosomally mediated fluoroquinolone resistance determinants were electroporated with pBK-CMV vector encoding QepA2. The MICs of fluoroquinolones were determined by standardized microdilution. The mutant prevention concentration (MPC) was evaluated. Bacterial fitness was analysed using ΔlacZ system competition assays.

RESULTS:

The ciprofloxacin MIC for strains harbouring the qepA2 gene was 4- to 8-fold higher compared with strains without the qepA2 gene. The qepA2 gene also increased the MPC of ciprofloxacin 4- to 16-fold. Combination of the qepA2 gene plus two to three additional mechanisms conferred a clinically relevant resistance level. The presence of the qepA2 gene was associated with fitness costs in strains with mutations in the gyrA and/or parC genes, although the presence of an additional deletion of the marR gene compensated for this fitness cost by increasing bacterial fitness by 5%-23%.

CONCLUSIONS:

The additive effect of chromosomally mediated fluoroquinolone resistance mechanisms and the qepA2 gene led to clinical levels of fluoroquinolone resistance. Under competitive conditions, the qepA2 gene had a biological cost in E. coli that was compensated for by the presence of an additional deletion in the marR gene.

KEYWORDS:

E. coli; qepA; resistance mechanisms

PMID:
26041043
DOI:
10.1093/jac/dkv144
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center