Genotypic Diversity of Ciprofloxacin Nonsusceptibility and Its Relationship with Minimum Inhibitory Concentrations in Nontyphoidal Salmonella Clinical Isolates in Taiwan

Abstract

This study analyzed the genetic diversity of ciprofloxacin (CIP) nonsusceptibility and the relationship between two major mechanisms and minimum inhibitory concentrations (MICs) of CIP in nontyphoidal Salmonella (NTS). Chromosomal mutations in quinolone resistance-determining regions (QRDRs) and plasmid-mediated quinolone resistance (PMQR) genes were searched from ResFinder, ARG-ANNOT, and PubMed for designing the sequencing regions in gyrA, gyrB, parC, and parE, and the 13 polymerase chain reactions for PMQR genes. We found that QRDR mutations were detected in gyrA (82.1%), parC (59.0%), and parE (20.5%) but not in gyrB among the 39 isolates. Five of the 13 PMQR genes were identified, including oqxA (28.2%), oqxB (28.2%), qnrS (18.0%), aac(6′)-Ib-cr (10.3%), and qnrB (5.1%), which correlated with the MICs of CIP within 0.25–2 μg/mL, and it was found that oxqAB contributed more than qnr genes to increase the MICs. All the isolates contained either QRDR mutations (53.8%), PMQR genes (15.4%), or both (30.8%). QRDR mutations (84.6%) were more commonly detected than PMQR genes (46.2%). QRDR mutation numbers were significantly associated with MICs (p < 0.001). Double mutations in gyrA and parC determined high CIP resistance (MICs ≥ 4 μg/mL). PMQR genes contributed to intermediate to low CIP resistance (MICs 0.25–2 μg/mL), thus providing insights into mechanisms underlying CIP resistance.

Transcriptional Regulation and Functional Characterization of the Plasmid-Borne oqxAB Genes in Salmonella Typhimurium

“…The CIP MIC of S. Typhimurium PY1 carrying this construct was 0.0312 μg/mL, i.e., only a 2-fold increase compared with that of the vector control, indicating that aac(6′)-Ib-cr itself did not actually confer intermediate resistance (MIC ≥ 0.5 μg/mL) to ciprofloxacin. Such a phenomenon has also been reported in previous studies ( 13 , 14 ). S. Typhimurium PY1 carrying pAAC-AB, pAAC-ABRp, and pAAC-ABRc exhibited CIP MICs of 0.0312, 0.25, and 0.0625 μg/mL respectively.…”

The Mechanisms Involved in the Fluoroquinolone Resistance of Salmonella enterica Strains Isolated from Humans in Poland, 2018–2019: The Prediction of Antimicrobial Genes by In Silico Whole-Genome Sequencing

“…Moreover, mutation Thr57→Ser in ParC was the only substitution detected among 47 tested Salmonella strains with ciprofloxacin MIC range 0.125–0.25 mg/L in S. Hadar , (0.19–0.75 mg/L) in S. Newport and (0.25–3 mg/L) in S. Infantis , respectively. This is in line with the reports of other authors that found Thr57Ser as the most prevalent mutation in ParC in NTS human isolates [ 14 , 24 , 25 ]. In accordance with a recent study, the ParC mutation at Thr57→Ser was detected as the main substitution in Salmonella enterica isolates from food-producing animals in China with a broad range of the ciprofloxacin MIC value (0.008–64 mg/L) [ 26 ].…”

“…Additionally, since the late 1990s, three types of plasmid-mediated quinolone resistance (PMQR) mechanisms have been identified: Qnr, which protects target enzymes; AAC(6’)-Ib-cr, which mediates the acetylation of certain quinolones; QepA and OqxAB, which produce mobile efflux pumps [ 13 ]. Although PMQRs alone are considered factors that can provide only a low level of resistance, their presence may aid bacteria to survive under low FQ pressure sufficiently to develop mutations in the DNA gyrase and/or topoisomerase IV genes, and to acquire high-level resistance to FQs [ 14 ]. These molecular mechanisms can be accumulative and together influence the observed FQ minimum inhibitory concentration (MIC) value.…”

“…These molecular mechanisms can be accumulative and together influence the observed FQ minimum inhibitory concentration (MIC) value. The genotypic features of ciprofloxacin non-susceptibility caused by the QRDR mutations and the PMQR mechanisms among NTS human isolates can vary in time and countries, but most frequently are attributable to the GyrA mutations in 83 and/or 87 codon and/or the ParC substitution in 80 codon and PMQR presence, mainly Qnr [ 14 ].…”

Whole Genome Sequencing, Antibiotic Resistance, and Epidemiology Features of Nontyphoidal Salmonella Isolated From Diarrheic Children: Evidence From North China

“…According to the data (Hopkins et al, 2005 ; Zhan et al, 2019 ), mutations in chromosome and plasmid-mediated resistance genes all contributed to quinolones resistance, which is commonly used quinolones for Salmonellosis . Similar to a previous report in Taiwan (Fang et al, 2021 ), mutations in parC and gyrA were more likely to cause the resistance of quinolones.…”