<p>Emergence of <em>vanA</em>-Type Vancomycin-Resistant <em>Enterococcus faecium</em> ST 78 Strain with a rep2-Type Plasmid Carrying a Tn1546-Like Element Isolated from a Urinary Tract Infection in China</p>

Abstract

The emergence of vancomycin-resistant enterococci (VRE) dramatically narrows therapeutic options. Although the prevalence of VRE in China has maintained a low level, VRE outbreaks have been reported in some tertiary hospitals in the developed areas of China. The clonal background of vanA-positive Enterococcus faecium strains has not been well characterized in China. Here, we report the whole-genome sequence of a vanA-type vancomycin-resistant E. faecium belonging to sequence type (ST) 78 isolated from a urinary tract infection in China. Patients and Methods: A vancomycin-resistant E. faecium was isolated from a 66-year-old male patient diagnosed with brainstem hemorrhage. Antibiotic susceptibility assays were performed according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Complete genome sequencing was performed using both the HiSeq TM 4000 platform and the MinION platform. Plasmid, genomic and phylogenetic relationship analysis were further performed. Results: E. faecium VRE1 was resistant to all antimicrobials tested except for tetracyclines and oxazolidinones. The whole genome of E. faecium VRE1 was composed of one chromosomal DNA and four plasmids. Two virulence genes and five antimicrobial resistance genes were identified. In silico multilocus sequence typing (MLST) showed that it belonged to ST78 (clonal complex CC17), a well-known epidemic clone that is widespread in Europe and the United States. Three antimicrobial resistance genes, including aminoglycoside resistance genes ant(6)-Ia and aph(3ʹ)-III ; and glycopeptide resistance gene vanA, were located on a rep2-type plasmid carrying a Tn1546like element that has not been reported. The most closely related strain harboring a similar plasmid backbone was recovered from fodder sample in China that differed by 178 cgMLST loci. Conclusion: Our study characterizes the genomic feature of a vancomycin-resistant E. faecium ST78 strain harboring a vanA-carrying plasmid in China. The ST78 clonal group possessed the potential to emerge as a successful vanA-carrying epidemic lineage in China.

Genomic Characterization of a Vancomycin-Resistant Strain of Enterococcus faecium Harboring a rep2 Plasmid

“…Previous research found that rep2-type vanA-carrying plasmids are present in both Germany 35 and Hangzhou, China. 15 This study's findings, in combination with data that demonstrate the plasmid's wide prevalence, particularly in Hangzhou.…”

“…9,10 Several studies have been conducted to investigate the prevalence of vancomycin-resistant E. faecium (VREfm) in clinical settings in China, with considerable variation among the VREfm strains; ST78 and ST192 being the most frequently identified. [11][12][13][14][15] So far, the vanA and vanM determinants are the primary determinants of resistance to vancomycin. Understanding the dissemination of VREfm strains is important to comprehending the dynamics of how VRE emerges and spreads in hospital environments.…”

New Mutations in cls Lead to Daptomycin Resistance in a Clinical Vancomycin- and Daptomycin-Resistant Enterococcus faecium Strain

“…Only pEF332-2 and pEF332-4 are antibiotic-resistant plasmids. While pEF332-4 only carries ARGs for aminoglycosides and was previously found in E. faecium VRE1 ( Sun et al, 2020 ), pEF332-2 is a new plasmid that carries both vanA and vanM gene clusters. To the best of our knowledge, plasmids carrying both vanA and vanM genes are very rare, and only one such plasmid (pELF1) has been found so far in Japan, which is associated with high vancomycin resistance and high risk of transmission ( Hashimoto et al, 2019 ).…”

“…Further phylogenetic analysis of E. faecium EF332 plasmids and 55 other plasmids, along with subtyping of pEF332-2 with PlasmidFinder, suggests pEF332-2 belongs to type rep2 ( Figure 2 ). Previous report suggested type rep2 plasmids originate from a variety of sources, including hospitals, poultry, and foods ( Schwarz et al, 2001 ; Sletvold et al, 2007 ; Sun et al, 2020 ), suggesting that these plasmids may spread between multiple environments. Nevertheless, attempts to transfer pEF332-2 from the host E. faecium EF332 strain to another bacterium via conjugation or transformation were unsuccessful, showing the limited efficiency of horizontal gene transfer.…”

Effective Treatment of Skin Wounds Co-Infected with Multidrug-Resistant Bacteria with a Novel Nanoemulsion

“…However, vancomycin-resistant enterococci, first observed in the 1990s, has led to a significant rise in clinical VRE infections. This has progressed to the point that VRE is now categorized as a priority pathogen by The World Health Organization and a top antibiotic resistance threat by the Centers for Disease Control and Prevention ( 2 , 4 – 7 ). VRE has limited treatment options in chronic wounds and increased infection-related mortality, which are magnified in patients with compromised immune systems ( 2 , 4 , 8 – 11 ).…”