Clinical characteristics, specific resistance patterns, and molecular mechanisms of carbapenem-resistant Morganella morganii isolates.

IF 4.8 2区 医学 Q2 IMMUNOLOGY
Frontiers in Cellular and Infection Microbiology Pub Date : 2025-09-05 eCollection Date: 2025-01-01 DOI:10.3389/fcimb.2025.1672736
Xiangkuo Zheng, Weiliang Zeng, Yan Liu, Luozhu Feng, Jiayin Zheng, Tieli Zhou, Changrui Qian, Cui Zhou
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引用次数: 0

Abstract

Objectives: The emergence and spread of carbapenem-resistant Morganella morganii (M. morganii) pose a serious global challenge. This study aimed to investigate the clinical characteristics, resistance patterns, and molecular mechanisms of carbapenem-resistant M. morganii.

Methods: A total of 170 M. morganii clinical isolates were collected from the First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China) between January 2016 and December 2017. Carbapenem MICs were determined by antimicrobial susceptibility testing. Carbapenem resistance determinants, including carbapenemase genes (bla KPC-2, bla VIM, bla IMP, bla NDM, and bla OXA-48) and extended-spectrum β-lactamase (ESBL) genes (bla TEM, bla CTX-M-1, and bla SHV), were analyzed by polymerase chain reaction (PCR). PCR and sequencing assays were performed to detect penicillin-binding protein (PBP) mutations. Efflux pump activity was also assessed in carbapenem-resistant isolates. Quantitative real-time PCR (qRT-PCR) was used to determine the relative mRNA expression levels of outer membrane porin-encoding gene ompC and PBP activator-encoding genes lpoA and lpoB.

Results: Twenty-six imipenem-resistant and 108 imipenem-intermediate M. morganii isolates were identified, accounting for 15.29% and 63.53% of cases, respectively. No isolates were resistant to meropenem or ertapenem. Among the 26 carbapenem-resistant isolates, the prevalence of ESBL genes bla TEM and bla CTX-M-1 was 30.77% and 11.54%, respectively, while carbapenemase genes were not detected. Resistant isolates carried more specific PBP mutations than carbapenem-susceptible and carbapenem-intermediate isolates. Efflux pump phenotypes were associated with reduced imipenem susceptibility in 13 carbapenem-resistant isolates. qRT-PCR revealed no significant differences in ompC expression among the resistant, intermediate, and susceptible groups; however, significant differences were observed in lpoA and lpoB expression. Isolates in the imipenem-resistant group carried more PBP mutations.

Conclusion: M. morganii isolates were commonly non-susceptible to imipenem but remained susceptible to meropenem and ertapenem. Low expression of PBP activator genes (lpoA and lpoB), along with the presence of specific PBP mutations, appeared to be the primary mechanisms of resistance. In addition, efflux pump overexpression may contribute to imipenem resistance in M. morganii.

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耐碳青霉烯摩氏摩根菌分离株的临床特征、特异性耐药模式和分子机制。
目的:耐碳青霉烯摩根摩根菌的出现和传播构成了一个严重的全球性挑战。本研究旨在探讨耐碳青霉烯型莫氏分枝杆菌的临床特征、耐药模式和分子机制。方法:2016年1月至2017年12月在温州医科大学第一附属医院收集临床分离的莫氏分枝杆菌170株。采用药敏试验测定碳青霉烯类MICs。采用聚合酶链反应(PCR)分析碳青霉烯类耐药决定因素,包括碳青霉烯酶基因(bla KPC-2、bla VIM、bla IMP、bla NDM和bla OXA-48)和广谱β-内酰胺酶基因(bla TEM、bla CTX-M-1和bla SHV)。PCR和测序检测青霉素结合蛋白(PBP)突变。对碳青霉烯耐药菌株的外排泵活性也进行了评估。采用实时荧光定量PCR (qRT-PCR)检测外膜孔蛋白编码基因ompC和PBP激活子编码基因lpoA和lpoB的相对mRNA表达量。结果:共检出耐亚胺培南莫氏分枝杆菌26株,占病例总数的15.29%,亚胺培南中间体莫氏分枝杆菌108株,占病例总数的63.53%。没有分离株对美罗培南和厄他培南耐药。在26株碳青霉烯耐药菌株中,ESBL基因bla TEM和bla CTX-M-1的检出率分别为30.77%和11.54%,碳青霉烯酶基因未检出。耐药菌株比碳青霉烯敏感菌株和碳青霉烯中间菌株携带更多特异性PBP突变。外排泵表型与13株碳青霉烯耐药菌株亚胺培南敏感性降低相关。qRT-PCR结果显示,耐药组、中间组和易感组的ompC表达无显著差异;而lpoA和lpoB的表达差异有统计学意义。耐亚胺培南组的分离株携带更多的PBP突变。结论:莫氏分枝杆菌对亚胺培南不敏感,但对美罗培南和厄他培南敏感。PBP激活基因(lpoA和lpoB)的低表达,以及特异性PBP突变的存在,似乎是抗性的主要机制。此外,外排泵过表达可能有助于摩根氏分枝杆菌对亚胺培南的耐药。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.90
自引率
7.00%
发文量
1817
审稿时长
14 weeks
期刊介绍: Frontiers in Cellular and Infection Microbiology is a leading specialty journal, publishing rigorously peer-reviewed research across all pathogenic microorganisms and their interaction with their hosts. Chief Editor Yousef Abu Kwaik, University of Louisville is supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Cellular and Infection Microbiology includes research on bacteria, fungi, parasites, viruses, endosymbionts, prions and all microbial pathogens as well as the microbiota and its effect on health and disease in various hosts. The research approaches include molecular microbiology, cellular microbiology, gene regulation, proteomics, signal transduction, pathogenic evolution, genomics, structural biology, and virulence factors as well as model hosts. Areas of research to counteract infectious agents by the host include the host innate and adaptive immune responses as well as metabolic restrictions to various pathogenic microorganisms, vaccine design and development against various pathogenic microorganisms, and the mechanisms of antibiotic resistance and its countermeasures.
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