TY - JOUR AU - Su, Rina AU - Peng, Yunzhi AU - Wang, Zhanli AU - Yu, Hui AU - Wu, Qi PY - 2021/10/12 Y2 - 2024/03/29 TI - Identification of two novel type II topoisomerase mutations in Enterococcus spp. isolated from a hospital in China JF - Archives of Biological Sciences JA - Arch Biol Sci VL - 73 IS - 3 SE - Articles DO - 10.2298/ABS210628034S UR - https://serbiosoc.org.rs/arch/index.php/abs/article/view/6731 SP - 407-414 AB - <p><strong>Paper description:</strong></p><ul><li>The mutational status of type II topoisomerases and the relationship of mutations with quinolone resistance is incompletely understood.</li><li>DNA sequencing was performed to investigate the mutational status of the quinolone resistance-determining regions of type II topoisomerases in clinical isolates of enterococci.</li><li>Two novel substitutions of <em> faecalis</em> were identified. Three-dimensional modeling revealed that these novel amino acid substitutions disrupt the water/metal-ion bridge and decrease the interaction between enzymes and ciprofloxacin.</li><li>These results elucidate the mechanisms of type II topoisomerase-mediated quinolone resistance in clinical isolates of enterococci.</li></ul><p><strong>Abstract: </strong>Type II topoisomerases, including DNA gyrase (GyrA) and topoisomerase IV (ParC), contribute to fluoroquinolone resistance in <em>Enterococcus</em> spp. This study investigated the mutational status of the quinolone resistance-determining regions (QRDRs) of GyrA and ParC in the clinical isolates of enterococci from a hospital in Baotou, China. We analyzed 110 enterococcal isolates, including 57 <em>Enterococcus faecalis</em> and 53 <em>Enterococcus faecalis faecium</em>. The resistance rates of <em>E. faecalis</em> and <em>E. faecium</em> to ciprofloxacin were 63.16% and 84.91%, respectively. We found that 32 samples of <em>E. faecalis</em> and 42 of <em>E. faecium</em> had single or combined mutations in <em>gyrA</em> and/or <em>parC</em>, which were all resistant to ciprofloxacin. Only two ciprofloxacin-resistant<em> E. faecalis</em> isolates had no mutation. No mutations in <em>gyrA</em> and <em>parC</em> genes in all ciprofloxacin-susceptible isolates were found. 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 <em>gyrA</em> and <em>parC</em> were correlated with MIC elevation. Two novel substitutions (GyrA Ser83Phe and ParC Ser80Leu) of <em>E. faecalis</em> were identified herein. 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. The data showed a diversity of mutation types in QRDRs of type II topoisomerases whose association with fluoroquinolone resistance in clinical isolates of enterococci warrants further investigation.</p> ER -