Departments of Ophthalmology, Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
Infectious Disease & Microbiome Program, The Broad Institute, Cambridge, MA, USA.
J Antimicrob Chemother. 2018 Jun 1;73(6):1479-1486. doi: 10.1093/jac/dky039.
Vancomycin-resistant Enterococcus faecium is a leading cause of MDR hospital infection. Two genetically definable populations of E. faecium have been identified: hospital-adapted MDR isolates (clade A) and vancomycin-susceptible commensal strains (clade B). VanN-type vancomycin resistance was identified in two isolates of E. faecium recovered from blood and faeces of an immunocompromised patient. To understand the genomic context in which VanN occurred in the hospitalized patient, the risk it posed for transmission in the hospital and its origins, it was of interest to determine where these strains placed within the E. faecium population structure.
We obtained the genome sequence of the VanN isolates and performed comparative and functional genomics of the chromosome and plasmid content.
We show that, in these strains, VanN occurs in a genetic background that clusters with clade B E. faecium, which is highly unusual. We characterized the chromosome and the conjugative plasmid that carries VanN resistance in these strains, pUV24. This plasmid exhibits signatures of in-host selection on the vanN operon regulatory system, which are associated with a constitutive expression of vancomycin resistance. VanN resistance in clade B strains may go undetected by current methods.
We report a case of vancomycin resistance in a commensal lineage of E. faecium responsible for an atypical bacteraemia in an immunocompromised patient. A reservoir of transferable glycopeptide resistance in the community could pose a concern for public health.
屎肠球菌是导致耐多药医院感染的主要原因。屎肠球菌已确定有两种遗传上可定义的种群：医院适应的多药耐药株（A 群）和对万古霉素敏感的共生菌株（B 群）。从一名免疫功能低下患者的血液和粪便中分离出的 2 株屎肠球菌，鉴定出 VanN 型万古霉素耐药。为了了解 VanN 在住院患者中发生的基因组环境，了解其在医院传播的风险及其来源，我们有兴趣确定这些菌株在屎肠球菌种群结构中的位置。
我们获得了 VanN 分离株的基因组序列，并对染色体和质粒内容进行了比较和功能基因组学分析。
我们表明，在这些菌株中，VanN 发生在与 B 群屎肠球菌聚类的遗传背景中，这非常罕见。我们对这些菌株中的染色体和携带 VanN 耐药性的可接合质粒 pUV24 进行了特征描述。该质粒在 vanN 操纵子调控系统上表现出与宿主选择相关的特征，这与万古霉素耐药性的组成型表达有关。B 群菌株中的 VanN 耐药性可能无法被当前方法检测到。
我们报告了一例对万古霉素耐药的共生谱系屎肠球菌，该菌株导致一名免疫功能低下患者出现非典型菌血症。社区中存在可转移糖肽类药物耐药性的储库可能会对公共卫生构成威胁。
