Hashimoto Yusuke, Hisatsune Junzo, Suzuki Masato, Kurushima Jun, Nomura Takahiro, Hirakawa Hidetada, Kojima Naoko, Ono Yuichi, Hasegawa Yutaka, Tanimoto Koichi, Sugai Motoyuki, Tomita Haruyoshi
Department of Bacteriology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Department of Antimicrobial Resistance, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
JAC Antimicrob Resist. 2022 Jan 4;4(1):dlab189. doi: 10.1093/jacamr/dlab189. eCollection 2022 Mar.
VanD is a rare type of vancomycin resistance worldwide. However, the host diversity of the gene cluster and the structural similarity of their genomic islands are not well understood.
Three VanD-type strains (AA620, AA622 and AA624) isolated from a Japanese patient who underwent vancomycin treatment in 2017 were analysed. This study utilized WGS analysis to characterize the three VanD-type strains and describes the diversity of hosts possessing VanD-carrying genomic islands.
The three isolates exhibited variable MICs of vancomycin. In the relatively vancomycin-resistant AA620, mutations were identified in and . The strains AA622 and AA624 had intact and harboured two gene clusters. qRT-PCR results revealed the mutation to be a factor affecting the high vancomycin resistance range of AA620. WGS data showed the 155 kb and 185 kb genomic islands harbouring the gene cluster inserted in the coding region of the gene, located in the chromosome in AA620 and AA622/624, respectively. Comparing the VanD-carrying genomic islands to available sequences of other enterococci and enteric anaerobes revealed how the genomic islands of these organisms isolated worldwide shared similar core genes and backbones. These anaerobes belonged to various genera within the order Eubacteriales. The phylogenetic cluster of the genomic island core genome alignment did not correlate with the host-species lineage, indicating horizontal gene transfer in the gut microbiota.
By horizontal gene transfer, various bacteria forming the gut microbiota maintain VanD-carrying genomic islands.
VanD是一种在全球范围内罕见的万古霉素耐药类型。然而,其基因簇的宿主多样性及其基因组岛的结构相似性尚未得到充分了解。
对2017年接受万古霉素治疗的一名日本患者分离出的三株VanD型菌株(AA620、AA622和AA624)进行了分析。本研究利用全基因组测序(WGS)分析对这三株VanD型菌株进行特征描述,并描述了携带VanD的基因组岛的宿主多样性。
这三株分离株对万古霉素表现出不同的最低抑菌浓度(MIC)。在相对耐万古霉素的AA620中,在[具体基因1]和[具体基因2]中发现了突变。AA622和AA624菌株的[具体基因1]和[具体基因2]完整,并含有两个[具体基因簇]。定量逆转录聚合酶链反应(qRT-PCR)结果显示,[具体基因1]突变是影响AA620高万古霉素耐药范围的一个因素。WGS数据显示,在AA620和AA622/624中,分别位于染色体上的[具体基因]编码区插入了携带[具体基因簇]的155 kb和185 kb基因组岛。将携带VanD的基因组岛与其他肠球菌和肠道厌氧菌的可用序列进行比较,揭示了全球分离的这些生物体的基因组岛如何共享相似的核心基因和主干。这些厌氧菌属于真杆菌目内的不同属。基因组岛核心基因组比对的系统发育簇与宿主物种谱系不相关,表明肠道微生物群中存在水平基因转移。
通过水平基因转移,构成肠道微生物群的各种细菌维持着携带VanD的基因组岛。