Dissemination and genetic analysis of the stealthy vanB gene clusters of Enterococcus faecium clinical isolates in Japan

BMC Microbiology

Yusuke Hashimoto¹  Jun Kurushima²  Takahiro Nomura³  Koichi Tanimoto⁴ 

[1] Department of Bacteriology, Gunma University Graduate School of Medicine, Maebashi, Japan;Laboratory of Bacterial Drug Resistance, Gunma University Graduate School of Medicine, Maebashi, Japan;MIROKU Medical Laboratory Inc, Nagano, Japan;Yamaguchi Prefectural Institute of Public Health and Environment, Yamaguchi, Japan

关键词: VRE;    Antibiotic resistance;    Outbreak;    Conjugation;    Reversion;   

DOI  :  10.1186/s12866-018-1342-1

学科分类：微生物学和免疫学

来源: BioMed Central

【 摘 要 】

VanB-type vancomycin (VAN) resistance gene clusters confer VAN resistances on Enterococcus spp. over a wide range of MIC levels (MIC = 4–1000 mg/L). However, the epidemiology and the molecular characteristics of the VAN susceptible VanB-type Enterococcus still remain unclear. We characterized 19 isolates of VanB-type Enterococcus faecium that might colonize in the gut and were not phenotypically resistant to VAN (MIC = 3 mg/L). They were obtained from two hospitals in Japan between 2009 and 2010. These isolates had the identical vanB gene cluster and showed same multilocus sequence typing (MLST) (ST78) and the highly related profiles in pulsed-field gel electrophoresis (PFGE). The vanB gene cluster was located on a plasmid, and was transferable to E. faecium and E. faecalis. Notably, from these VanB-type VREs, VAN resistant (MIC≥16 mg/L) mutants could appear at a frequency of 10− 6–10− 7/parent cell in vitro. Most of these revertants acquired mutations in the vanSB gene, while the remainder of the revertants might have other mutations outside of the vanB gene cluster. All of the revertants we tested showed increases in the VAN-dependent expression of the vanB gene cluster, suggesting that the mutations affected the transcriptional activity and increased the VAN resistance. Targeted mutagenesis revealed that three unique nucleotide substitutions in the vanB gene cluster of these strains attenuated VAN resistance. In summary, this study indicated that stealthy VanB-type E. faecium strains that have the potential ability to become resistance to VAN could exist in clinical settings.

【 授权许可】

CC BY