Cytotoxic Effect Associated with Overexpression of QNR Proteins in Escherichia coli

Jesús Machuca1,2, Paula Diaz de Alba1, Esther Recacha1

  • 11 Unidad Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena , Seville, Spain .

Microbial Drug Resistance (Larchmont, N.Y.)
|March 14, 2017
PubMed
Abstract

Insights

Overexpressing Qnr genes in Escherichia coli causes significant bacterial death and cell damage, unlike QepA2. This cytotoxicity varies by Qnr protein family.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacterial Genetics

Background:

  • Quinolone resistance in bacteria is a growing public health concern.
  • Plasmid-mediated quinolone resistance (PMQR) mechanisms contribute to reduced susceptibility to fluoroquinolone antibiotics.
  • The cytotoxic effects of PMQR gene overexpression in bacteria are not fully understood.

Purpose of the Study:

  • To investigate the cytotoxic impact of overexpressing various Qnr-like PMQR mechanisms in Escherichia coli.
  • To compare the cytotoxic effects of different Qnr families and the QepA2 efflux pump.

Main Methods:

  • Cloning and overexpression of PMQR genes (qnrA1, qnrB1, qnrC, qnrD1, qnrS1, qepA2, efsqnr) in E. coli BL21.
  • Utilizing E. coli BL21 with and without an empty vector as controls.
  • Assessing cytotoxicity via transmission electron microscopy and bacterial viability assays.

Main Results:

  • Overexpression of qnr genes led to significant bacterial viability loss (77-97%), similar to EfsQnr (97%).
  • No viability loss was observed with QepA2 overexpression.
  • Transmission electron microscopy revealed morphological changes in 30-45% of cells overexpressing EfsQnr and Qnr proteins, compared to <5% in controls and QepA2-overexpressing cells.

Conclusions:

  • Overexpression of qnr genes induces a cytotoxic cellular and structural effect in E. coli.
  • The extent of cytotoxicity is dependent on the specific Qnr protein family involved.