Working Paper Article Version 1 This version is not peer-reviewed

Type II Topoisomerase Mutations in Enterococcus spp. Isolated from a Hospital in Baotou, China

Version 1 : Received: 6 August 2020 / Approved: 6 August 2020 / Online: 6 August 2020 (10:34:40 CEST)

How to cite: Yu, H.; Peng, Y.; Liu, Y.; Liu, M.; Wang, Z. Type II Topoisomerase Mutations in Enterococcus spp. Isolated from a Hospital in Baotou, China. Preprints 2020, 2020080154 Yu, H.; Peng, Y.; Liu, Y.; Liu, M.; Wang, Z. Type II Topoisomerase Mutations in Enterococcus spp. Isolated from a Hospital in Baotou, China. Preprints 2020, 2020080154

Abstract

Type II Topoisomerases, including DNA gyrase (GyrA) and topoisomerase IV (ParC), contribute to fluoroquinolone resistance in Enterococcus spp. This study investigated the mutational status of the quinolone resistance-determining regions (QRDRs) of GyrA and ParC among the clinical isolates of enterococci from a hospital in Baotou, China. We analyzed 110 enterococcal isolates, including 57 E. faecalis and 53 E. faecium. The resistance rates of E. faecalis and E. faecium to ciprofloxacin were 63.16 % and 84.91 %, respectively. Additionally, we found 32 E. faecalis and 42 E. faecium had single or combined mutations in gyrA and/or parC, which were all resistant to ciprofloxacin. Only two ciprofloxacin-resistant E. faecalis isolates had no mutation. We did not find mutations in gyrA and parC genes for all ciprofloxacin- susceptible isolates. Our results further demonstrated that ciprofloxacin minimal inhibitory concentrations (MICs) in the mutation group were significantly higher than those of the non-mutation group, indicating that mutations in the QRDRs of gyrA and parC genes were correlated with MIC elevations. Moreover, the present study identified for the first time, to the best of our knowledge, two novel substitutions (GyrA Ser83Phe and ParC Ser80Leu) of E. faecalis. Three-dimensional modeling revealed that these novel amino acid substitutions could disrupt the water/metal-ion bridge and decrease the interaction between the enzymes and ciprofloxacin. These data imply that identification of mutations in QRDRs of type II topoisomerases can be used to manage fluoroquinolone-resistant enterococcal infections.

Subject Areas

enterococcus spp; type II topoisomerase; GyrA; ParC; fluoroquinolone resistance

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