Emergence of the mobile RND-type efflux pump gene cluster tmexCD1-toprJ1 in Klebsiella pneumoniae clinical isolates in Japan.

IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Journal of Antimicrobial Chemotherapy Pub Date : 2024-11-06 DOI:10.1093/jac/dkae395
Aki Hirabayashi, Hirokazu Yano, Koji Yahara, Sadao Aoki, Yo Sugawara, Toshiki Kajihara, Naomi Shibayama, Shizuo Kayama, Masato Suzuki, Motoyuki Sugai
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Abstract

Background: Tigecycline is an antimicrobial agent with a broad spectrum of activity against both Gram-positive and Gram-negative bacteria. However, mobile tigecycline resistance gene clusters, such as tnfxB-tmexCD-toprJ, have spread globally. The prevalence of tigecycline-resistant Enterobacterales in clinical settings in Japan is unknown.

Objectives: To investigate the tnfxB-tmexCD-toprJ gene cluster in the genome sequences of Enterobacterales clinical isolates in Japan.

Methods: We investigated the tnfxB-tmexCD-toprJ cluster from the genome sequences of 5143 Enterobacterales isolates collected from 175 hospitals around Japan between 2019 and 2020 as part of a national genomic surveillance program for antimicrobial-resistant bacteria.

Results: The tnfxB1-tmexCD1-toprJ1 cluster was detected in two Klebsiella pneumoniae isolates in 2019. One isolate possessed a 299.4 kb IncFIB(K) plasmid, pJBBGAAF19431, and the other possessed a 224.9 kb IncHI1B/IncFIB(K) hybrid plasmid, pJBEAACG19501, co-carrying multiple antimicrobial resistance genes, including extended-spectrum β-lactamase genes, blaOXA-1 and blaCTX-M-27, respectively, along with tnfxB1-tmexCD1-toprJ1. The genetic context of the tnfxB1-tmexCD1-toprJ1-surrounding structure on pJBBGAAF19431 was similar to that of a K. pneumoniae plasmid pHNAH8I-1 from a chicken in China in 2017, and the cluster was embedded in an apparently intact mobile DNA element: strand-biased circularizing integrative element. The tnfxB1-tmexCD1-toprJ1 on pJBEAACG19501 was embedded in a Tn3 family transposon related to TnAs1. The plasmid pJBEAACG19501 was highly similar to that of K. pneumoniae, isolated from humans in China in 2021.

Conclusions: tmexCD-toprJ was present in Japan as of 2019. Even in Japan, where the clinical use of tigecycline is significantly rare, tmexCD-toprJ-harbouring multidrug-resistant Enterobacterales is a public health threat and requires continuous monitoring.

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日本肺炎克雷伯氏菌临床分离物中出现的移动 RND 型外排泵基因簇 tmexCD1-toprJ1。
背景:替加环素是一种抗菌剂,对革兰氏阳性菌和革兰氏阴性菌具有广谱抗菌活性。然而,诸如 tnfxB-tmexCD-toprJ 等流动的替加环素耐药基因簇已在全球蔓延。耐替加环素肠杆菌在日本临床环境中的流行情况尚不清楚:调查日本临床分离出的肠杆菌基因组序列中的 tnfxB-tmexCD-toprJ 基因簇:作为全国耐药菌基因组监测计划的一部分,我们对2019年至2020年间从日本175家医院采集的5143株肠杆菌分离株的基因组序列中的tnfxB-tmexCD-toprJ基因簇进行了调查:结果:2019 年在两个肺炎克雷伯菌分离株中检测到 tnfxB1-tmexCD1-toprJ1 簇。其中一个分离株含有299.4 kb IncFIB(K)质粒pJBBGAAF19431,另一个分离株含有224.9 kb IncHI1B/IncFIB(K)杂交质粒pJBEAACG19501,分别与tnfxB1-tmexCD1-toprJ1共同携带多种抗菌药耐药基因,包括广谱β-内酰胺酶基因blaOXA-1和blaCTX-M-27。pJBBGAAF19431上的tnfxB1-tmexCD1-toprJ1环绕结构的遗传背景与2017年中国鸡肺炎克雷伯菌质粒pHNAH8I-1相似,而且该基因簇嵌入了一个明显完整的移动DNA元件:链偏向环化整合元件。pJBEAACG19501上的tnfxB1-tmexCD1-toprJ1嵌入了与TnAs1相关的Tn3家族转座子。该质粒 pJBEAACG19501 与 2021 年从中国人体内分离出的肺炎双球菌质粒高度相似。即使在日本,替加环素的临床应用也非常罕见,但与 tmexCD-toprJ 相关的耐多药肠道杆菌仍是一种公共卫生威胁,需要持续监测。
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来源期刊
CiteScore
9.20
自引率
5.80%
发文量
423
审稿时长
2-4 weeks
期刊介绍: The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.
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