Genotypic Diversity of Ciprofloxacin Nonsusceptibility and Its Relationship with Minimum Inhibitory Concentrations in Nontyphoidal <i>Salmonella</i> Clinical Isolates in Taiwan
Shiuh-Bin Fang,
Tsai-Ling Yang Lauderdale,
Chih-Hung Huang,
Pei-Ru Chang,
Yuan-Hung Wang,
Katsumi Shigemura,
Ying-Hsiu Lin,
Wei-Chiao Chang,
Ke-Chuan Wang,
Tzu-Wen Huang,
Yu-Chu Chang
Affiliations
Shiuh-Bin Fang
Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
Tsai-Ling Yang Lauderdale
National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, Taiwan
Chih-Hung Huang
Graduate Institute of Biochemical and Biomedical Engineering, National Taipei University of Technology, Taipei 10608, Taiwan
Pei-Ru Chang
Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
Yuan-Hung Wang
Department of Medical Research, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
Katsumi Shigemura
Department of Urology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Ying-Hsiu Lin
Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
Wei-Chiao Chang
Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
Ke-Chuan Wang
Division of Pediatric Gastroenterology and Hepatology, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, New Taipei City 23561, Taiwan
Tzu-Wen Huang
Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
Yu-Chu Chang
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
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 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.
