Rapid Emergence of High-Level Resistance to Quinolones in Campylobacter jejuni Associated with Mutational Changes in gyrA and parC

Abstract

Quinolone resistance in clinical isolates of Campylobacter jejuni in Sweden increased more than 20-fold at the beginning of the 1990s. Resistance to 125 g of ciprofloxacin per ml in clinical isolates was associated with chromosomal mutations in C. jejuni leading to a Thr-86-Ile substitution in the gyrA product and a Arg-139-Gln substitution in the parC product.

Analysis of topoisomerase mutations in fluoroquinolone-resistant and -susceptible Campylobacter jejuni strains isolated in Senegal

“…To achieve high-level resistance to fluoroquinolones, additional mutations in the gyrA QRDR and/or gyrB gene or in topoisomerases IV (parC, parE) are required [8,9]. To date, no mutation in gyrB has been associated with fluoroquinolone resistance in C. jejuni [4,6] and the role of mutations in topoisomerase IV, previously reported [10], has not been confirmed by others studies. However, there has been one report describing mutations outside the GyrA QRDR (Asn203-Ser and/or Ala206-Thr) associated with fluoroquinolone resistance [11].…”

Antimicrobial susceptibility and mechanism of quinolone resistance in Campylobacter jejuni strains isolated from diarrheal patients in a hospital in Tokyo

“…5,7,[12][13][14] Thus, in the present study, to elucidate the mechanism of quinolone resistance, we investigated the presence of mutations in the QRDR of the gyrA gene. We found amino-acid substitution at codon 86 (Thr → IIe) in all the 37 strains showing resistance to CPFX; in contrast, such amino-acid substitution was not observed at codon 86 in any of the 18 strains susceptible to CPFX.…”

“…Therefore, increasing attention has been paid to the acquisition of resistance to quinolone agents by C. jejuni strains. 6,7 The mechanism of action of fl uoroquinolones against bacteria is through their specifi c binding to type II topoisomerase, which cuts and reanneals double-stranded DNA, thereby inhibiting the cutting of the DNA and the reannealing of the separated DNA. 8,9 Type II topoisomerases include DNA gyrase, which functions in the early phase of DNA replication, and topoisomerase IV, which is composed of ParC and ParE subunits and functions in the last phase of DNA replication.…”

Quinolone resistance in the food chain

“…It is recognised that Campylobacter, as well as other microorganisms such as Helicobacter pylori and Mycobacterium tuberculosis, do not have topoisomerase IV. No gene with homology to parC has been found in the Campylobacter genome, which may explain why a single mutation in gyrA can lead to a high level of resistance not only to nalidixic acid but also to ciprofloxacin [46][47][48][49][50][51][52].…”