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中国广东省临床耐碳青霉烯菌株的流行病学和遗传特征。

Epidemiological and Genetic Characteristics of Clinical Carbapenem-Resistant Strains in Guangdong Province, China.

机构信息

Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark.

Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

出版信息

Microbiol Spectr. 2023 Jun 15;11(3):e0426122. doi: 10.1128/spectrum.04261-22. Epub 2023 Apr 20.

Abstract

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a bacterial pathogen that may cause serious drug-resistant infections that are potentially fatal. To investigate the genetic characteristics of these organisms, we tested 416 P. aeruginosa strains recovered from 12 types of clinical samples collected in 29 different hospital wards in 10 hospitals in Guangdong Province, China, from 2017 to 2020. These strains were found to belong to 149 known sequence types (STs) and 72 novel STs, indicating that transmission of these strains involved multiple routes. A high rate of resistance to imipenem (89.4%) and meropenem (79.4%) and a high prevalence of pathogenic serotypes (76.4%) were observed among these strains. Six STs of global high-risk clones (HiRiCs) and a novel HiRiC strains, ST1971, which exhibited extensive drug resistance, were identified. Importantly, ST1971 HiRiC, which was unique in China, also exhibited high virulence, which alarmed the further surveillance on this highly virulent and highly resistant clone. Inactivation of the gene and overexpression of efflux systems were found to be mainly responsible for carbapenem resistance in these strains; carriage of metallo-β-lactamase (MBL)-encoding genes was less common. Interestingly, frameshift mutations (49.0%) and introduction of a stop codon (22.4%) into the genes were the major mechanisms of imipenem resistance. On the other hand, expression of the MexAB-OprM efflux pump and MBL-encoding genes were mechanisms of resistance in >70% of meropenem-resistant strains. The findings presented here provide insights into the development of effective strategies for control of worldwide dissemination of CRPA. Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a major concern in clinical settings worldwide, yet few genetic and epidemiological studies on CRPA strains have been performed in China. Here, we sequence and analyze the genomes of 416 P. aeruginosa strains from hospitals in China to elucidate the genetic, phenotypic, and transmission characteristics of CRPA strains and to identify the molecular signatures responsible for the observed increase in the prevalence of CRPA infections in China. These findings may provide new insight into the development of effective strategies for worldwide control of CRPA and minimize the occurrence of untreatable infections in clinical settings.

摘要

耐碳青霉烯铜绿假单胞菌(CRPA)是一种细菌病原体,可能导致严重的耐药性感染,甚至致命。为了研究这些生物体的遗传特征,我们测试了 2017 年至 2020 年间从中国广东省 10 家医院的 29 个不同病房的 12 种临床样本中收集的 416 株铜绿假单胞菌菌株。这些菌株属于 149 个已知的序列型(ST)和 72 个新的 ST,表明这些菌株的传播涉及多种途径。这些菌株对亚胺培南(89.4%)和美罗培南(79.4%)的耐药率较高,致病性血清型的流行率较高(76.4%)。鉴定出 6 种全球高危克隆(HiRiCs)的 ST 和一种新型 HiRiC 菌株 ST1971,该菌株表现出广泛的耐药性。重要的是,在中国特有的 ST1971 HiRiC 也表现出高毒力,这引起了对这种高毒力和高度耐药克隆的进一步监测。我们发现这些菌株的碳青霉烯耐药性主要与 基因失活和外排系统过度表达有关;携带金属β-内酰胺酶(MBL)编码基因的情况较少见。有趣的是,49.0%的菌株出现移码突变,22.4%的菌株 基因出现终止密码子,这是导致这些菌株对亚胺培南耐药的主要机制。另一方面,MexAB-OprM 外排泵和 MBL 编码基因的表达是 70%以上耐美罗培南菌株耐药的机制。本研究结果为制定有效的策略控制全球耐碳青霉烯铜绿假单胞菌的传播提供了新的思路。

耐碳青霉烯铜绿假单胞菌(CRPA)是全球临床关注的主要问题,但在中国开展的关于 CRPA 菌株的遗传和流行病学研究较少。在这里,我们对来自中国医院的 416 株铜绿假单胞菌进行了测序和分析,以阐明 CRPA 菌株的遗传、表型和传播特征,并确定导致中国 CRPA 感染流行率增加的分子特征。这些发现可能为制定有效的全球耐碳青霉烯铜绿假单胞菌控制策略提供新的思路,并最大限度地减少临床环境中无法治疗感染的发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0bd/10269565/2d867ad899b9/spectrum.04261-22-f001.jpg

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