Department of Laboratory Medicine, Tokyo Metropolitan Tama Medical Center, Tokyo, Japan.
Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Microbiol Spectr. 2024 Nov 5;12(11):e0052324. doi: 10.1128/spectrum.00523-24. Epub 2024 Sep 17.
The extended-spectrum β-lactamase (ESBL) gene, , was identified for the first time in an clinical isolate, JARB-RN-0061, from blood cultures in a Japanese general hospital in 2021. The isolate exhibited high resistance to broad-spectrum cephalosporins, including ceftazidime (MIC >128 mg/L) and cefepime (MIC = 16 mg/L). was identified during whole-genome sequencing and characterization of the isolate. JARB-RN-0061 belonged to the B2-O2:K1:H7-ST95-41 lineage and was classified as presumptive extraintestinal pathogenic (ExPEC) and uropathogenic (UPEC). Moreover, the strain harbored multiple virulence genes on the chromosome. The Col156/IncFIB(AP001918)/IncFII(29)-type plasmid (114,216 bp), with and genes involved in bacteremia, was unique to the 41 subclone. The gene was located on a non-typeable and non-conjugative plasmid, pJARB-RN-0061_VEB-1 (17,093 bp). It was embedded in the class 1 integron In1883-like, with multidrug resistance gene cassettes for , , , , and . Notably, comparative analysis of the complete sequence of plasmid pJARB-RN-0061_VEB-1 revealed that it was highly homologous to the -harboring plasmid, pMS2H7VEB-1 (100% coverage and 99.99% identity), except for the Tn3 family transposon (4,931 bp) and the plasmid pRHBSTW-00138_5 (97% coverage and 100% identity) harbored by subsp. strains from hospital sewage in Japan and wastewater influent in the United Kingdom, respectively. The emergence of a human pathogenic clinical isolate with the -carrying plasmid in the B2-ST95 worldwide pandemic lineage, characterized by the virulence potential of ExPEC or UPEC but a low prevalence of antimicrobial resistance, would raise public health concerns.
ESBLs are plasmid-mediated enzymes that confer resistance to clinically significant antimicrobial agents, such as broad-spectrum cephalosporins. Recently, the rapid spread of CTX-M-type ESBL-producing has become a global issue, including in Japan, where ESBL production in human pathogenic , such as the ExPEC and UPEC lineages, which typically harbor several virulence genes, is a severe public health concern. To date, VEB (Vietnamese extended-spectrum β-lactamase) producers have been found only in hospital wastewater and rivers in Japan. Thus, we describe the first detection of a very rare human-derived blaVEB-1 gene in the B2-ST95 pandemic clonal lineage that is highly associated with ExPEC and UPEC in a Japanese clinical setting. Furthermore, we characterized the genomic features of plasmids harboring the class 1 integron-borne blaVEB-1. Our findings highlight the significance of closely monitoring ESBL-producing isolates to prevent the potential dissemination of this resistance determinant in Japan.
扩展谱β-内酰胺酶（ESBL）基因，，于 2021 年首次在日本一家综合医院的血液培养物中从临床分离株 JARB-RN-0061 中鉴定出来。该分离株对包括头孢他啶（MIC>128mg/L）和头孢吡肟（MIC=16mg/L）在内的广谱头孢菌素表现出高度耐药性。在对分离株进行全基因组测序和表征时发现了。JARB-RN-0061 属于 B2-O2：K1：H7-ST95-41 谱系，被归类为推定的肠外致病性（ExPEC）和尿路致病性（UPEC）。此外，该菌株在染色体上携带多个毒力基因。Col156/IncFIB（AP001918）/IncFII（29）-型质粒（114216bp），带有与菌血症相关的和基因，是 41 亚克隆所特有的。基因位于非可分型和非可接合的质粒 pJARB-RN-0061_VEB-1（17093bp）上。它嵌入在类 1 整合子 In1883 样中，带有多种耐药基因盒，用于、、、和。值得注意的是，对质粒 pJARB-RN-0061_VEB-1 完整序列的比较分析表明，它与携带质粒 pMS2H7VEB-1 高度同源（100%覆盖和 99.99%同一性），除了 Tn3 家族转座子（4931bp）和质粒 pRHBSTW-00138_5（97%覆盖和 100%同一性）分别由日本医院污水中分离株和英国废水进水处的菌株携带。在全球大流行谱系 B2-ST95 中，人类致病性临床分离株出现携带质粒的情况令人担忧，该质粒携带 CTX-M 型 ESBL，具有 ExPEC 或 UPEC 的毒力潜力，但对多种抗菌药物的耐药率较低。
ESBLs 是一种质粒介导的酶，可赋予对临床重要抗菌药物的耐药性，如广谱头孢菌素。最近，CTX-M 型 ESBL 产生菌的快速传播已成为一个全球性问题，包括日本在内，在日本，人类致病性，如 ExPEC 和 UPEC 谱系，通常携带多个毒力基因，这是一个严重的公共卫生问题。迄今为止，VEB（越南扩展谱β-内酰胺酶）生产者仅在日本的医院废水和河流中被发现。因此，我们描述了首例在日本临床环境中非常罕见的人类衍生 blaVEB-1 基因在与 ExPEC 和 UPEC 高度相关的 B2-ST95 大流行克隆谱系中检测到。此外，我们对携带类 1 整合子的 blaVEB-1 的质粒的基因组特征进行了表征。我们的研究结果强调了密切监测产 ESBL 的菌的重要性，以防止这种耐药决定因素在日本的潜在传播。
