Predominance of III/ST19 and Ib/ST10 Lineages With High Multidrug Resistance in Fluoroquinolone-Resistant Group B Streptococci Isolates in Which a New Integrative and Conjugative Element Was Identified.

Kankan Gao,Qiulian Deng,Chien-Yi Chang,Haiying Liu,Lei Deng,Xiaoshan Guan,Fei Gao,David J Mciver,Lanlan Zeng,Wenjing Ji,Lianfen Huang,Huamin Zhong,Chunyan Gao,Yongqiang Xie

doi:10.3389/fmicb.2020.609526

Abstract

Fluoroquinolone (FQ)-resistant Group B Streptococcus (GBS) has been reported with considerable cross-resistance, worsening the crisis of multidrug-resistant (MDR) GBS in clinical settings. However, national epidemiological data on FQ-resistant GBS in mainland China have not been well-characterized. This study aimed to determine the prevalence of FQ resistance among GBS from neonatal invasive infections and maternal colonization in northern and southern China, to investigate the serotyping, multilocus sequence typing, and antibiotic cross-resistance, and to characterize the mutations in gyrA and parC genes in quinolone resistance-determining region (QRDR). In order to provide a comprehensive view of the location and structure of resistance genes, whole-genome sequencing on III/ST19 MDR isolates were performed. Among 426 GBS, 138 (32.4%) were FQ resistant, with higher prevalence in northern China than in southern China in both neonates (57.8%, 37/64 vs. 21.7%, 39/180) and pregnant women (50.9%, 29/57 vs. 26.4%, 33/125). Serotypes were distributed as III (48.5%), Ib (39.9%), V (6.5%), and Ia (5.1%). Sequence types were mainly ST19 (53.6%) and ST10 (39.1%), followed by ST12 (1.4%), ST17 (1.4%), ST23 (1.4%), and 0.7% each of ST27, ST188, ST197, and ST597. ST19 isolates were more prevalent in southern China than in northern China in both neonates (64.1%, 25/39 vs. 27.0%, 10/37) and pregnant women (81.8%, 27/33 vs. 41.4%, 12/29), whereas ST10 isolates were more common in northern China than in southern China in both neonates (64.9%, 24/37 vs. 20.5%, 8/39) and pregnant women (58.6%, 17/29 vs. 15.2%, 5/33). Serotype III isolates were mainly ST19 (89.6%, 60/67), while Ib isolates were largely ST10 (94.5%, 52/55). Sequencing data revealed several mutations in QRDR, including Ser81Leu in gyrA (99.2%, 130/131), Ser79Phe or Tyr in parC (76.2%, 48/63), and a previously unreported Ile218Thr and Ile219Phe double mutation pattern (49.2%, 31/63) in parC. ST10 isolates were associated with Ser79Phe (84%, 21/25), while ST19 isolates were limited to Ser79Tyr (95.7%, 22/23). A new integrative and conjugative element (ICE) harboring tetM and gyrA genes was identified in a III/ST19 isolate. This study investigates the molecular characteristics of FQ-resistant GBS in northern and southern China, emphasizing the need for continuous surveillance geographically and further research to characterize the mechanisms of ICE transfer.

Highlights

Group B Streptococcus (GBS), known as Streptococcus agalactiae, commonly colonizes the human gastrointestinal and genitourinary tracts (CDC, 2010) and has been recognized as the leading contributor to adverse maternal and neonatal outcomes (Seale et al, 2017; Zhang et al, 2019)
Intrapartum use of prophylactic antibiotics in pregnant women with GBS colonization has been shown to be very successful in reducing the incidence of early-onset GBS disease (CDC, 2010), but this strategy has not been fully adopted in mainland China
All 426 strains were sensitive to penicillin, ampicillin, vancomycin, tigecycline, and linezolid, and no penicillin susceptibility reduced GBS isolate was found

Summary

Introduction

Group B Streptococcus (GBS), known as Streptococcus agalactiae, commonly colonizes the human gastrointestinal and genitourinary tracts (CDC, 2010) and has been recognized as the leading contributor to adverse maternal and neonatal outcomes (Seale et al, 2017; Zhang et al, 2019). Intrapartum use of prophylactic antibiotics in pregnant women with GBS colonization has been shown to be very successful in reducing the incidence of early-onset GBS disease (CDC, 2010), but this strategy has not been fully adopted in mainland China. In mainland China, most FQ-resistant GBS strains have been isolated from urine and wounds (Wang et al, 2013). Little is known regarding the molecular epidemiology of FQ-resistant GBS isolated from neonatal invasive infections and maternal colonization nationwide. The horizontal transfer of mobile genetic elements (MGEs) via conjugation has been suggested as an important determinant of the dissemination of antibiotic resistance genes (Von Wintersdorff et al, 2016)

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