Impact of co-existence of PMQR genes and QRDR mutations on fluoroquinolones resistance in Enterobacteriaceae strains isolated from community and hospital acquired UTIs

Abstract

Background: Fluoroquinolones are commonly recommended as treatment for urinary tract infections (UTIs). The development of resistance to these agents, particularly in gram-negative microorganisms complicates treatment of infections caused by these organisms. This study aimed to investigate antimicrobial resistance of different Enterobacteriaceae species isolated from hospital- acquired and community-acquired UTIs against fluoroquinolones and correlate its levels with the existing genetic mechanisms of resistance.

Methods: A total of 440 Enterobacteriaceae isolates recovered from UTIs were tested for antimicrobial susceptibility. Plasmid-mediated quinolone resistance (PMQR) genes and mutations in the quinolone resistance-determining regions (QRDRs) of gyrA and parC genes were examined in quinolone-resistant strains.

Results: About (32.5%) of isolates were resistant to quinolones and (20.5%) were resistant to fluoroquinolones. All isolates with high and intermediate resistance phenotypes harbored one or more PMQR genes. QnrB was the most frequent gene (62.9%) of resistant isolates. Co-carriage of 2 PMQR genes was detected in isolates (46.9%) with high resistance to ciprofloxacin (CIP) (MICs > 128 μg/mL), while co-carriage of 3 PMQR genes was detected in (6.3%) of resistant isolates (MICs > 512 μg/mL). Carriage of one gene only was detected in intermediate resistance isolates (MICs of CIP = 1.5-2 μg/mL). Neither qnrA nor qnrC genes were detected. The mutation at code 83 of gyrA was the most frequent followed by Ser80-Ile in parC gene, while Asp-87 Asn mutation of gyrA gene was the least, where it was detected only in high resistant E. coli isolates (MIC ≥128 μg/mL). A double mutation in gyrA (Lys154Arg and Ser171Ala) was observed in high FQs resistant isolates (MIC of CIP < 128 μg/mL).

Conclusion: FQs resistance is caused by interact between PMQR genes and mutations in both gyrA and parC genes while a mutation in one gene only can explain quinolone resistance. Accumulation of PMQR genes and QRDR mutations confers high resistance to FQs.

Keywords: Enterobacteriaceae; Fluoroquinolones; Plasmid-mediated quinolone resistance; Quinolone resistance-determining regions (QRDRs).

Fig. 1

Alteration in gyr A (codon 83). Nucleotide sequence of a gyrA region of the E. coli FQs-susceptible, WP_074153749.1 DNA gyrase subunit A (E. coli). Alteration in (codon 83)

Fig. 2

Alteration in gyr A (codon 83, 154, 171). Nucleotide sequence of a gyrA region of the Citrobacter spp. high resistance isolates, WP_044266198.1 DNA gyrase subunit A (Citrobacter). Alteration in (codon 83, 154, 171)

Fig. 3

Alteration in gyr A (codon 87). Nucleotide sequence of a gyrA region of the E. coli high resistance isolates, WP_074153749.1 DNA gyrase subunit A (E. coli) Alteration in (codon 87)

Fig. 4

Alteration in par C (codon 83). Nucleotide sequence of a parC region of the E. coli high resistance isolates, Reference Sequence Strain. AML00471.1 DNA topoisomerase IV. Alteration in (codon 80)