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大肠杆菌分离株中磷霉素抗性基因的分子特征分析

Molecular characterisation of fosfomycin resistance genes in Escherichia coli isolates.

作者信息

Yag Funda, Sezgin Fikriye Milletli, Sevim Elif

机构信息

Department of Molecular Medicine, Kirsehir Ahi Evran University Health Sciences Institute, Kirsehir, Turkey.

Department of Medical Microbiology, Amasya University School of Medicine, Amasya, 05100, Turkey.

出版信息

Folia Microbiol (Praha). 2025 May 7. doi: 10.1007/s12223-025-01269-1.

DOI:10.1007/s12223-025-01269-1
PMID:40329018
Abstract

Fosfomycin is a well-known antibiotic that exhibits broad-spectrum activity against various bacterial pathogens, including gram-negative strains and some gram-positive strains such as staphylococci. The use of parenteral fosfomycin has been recently revised because the antibiotic has been found to effectively manage serious infections caused by multidrug-resistant pathogens. The occurrence of fosfomycin resistance could threaten the reintroduction of this antibiotic for the treatment of bacterial infections. In this study, a total of 24 fosfomycin-resistant Escherichia coli isolates obtained from urine samples were used to investigate the prevalence and molecular epidemiology of plasmid-mediated fosfomycin resistance genes. The replication origins of the conjugative and transformant plasmids obtained from the isolates were examined using the replication origin determination method based on the polymerase chain reaction (PCR). Through the PCR process performed with the fosA, fosA3, fosB, fosC, fosC2, and fosX genes to determine fosfomycin resistance, one out of 24 samples was found to be fosA3 gene-positive. A Class-1 integron gene was detected in three fosfomycin-resistant E. coli isolates, while no Class-2 integrons were detected in any isolate. The conjugation experiments demonstrated that the fosA3 gene was transferable in one isolate that also carried the blaTEM, blaCTX-M-15, and aac(6')-ib-cr genes. Through plasmid isolation in the transconjugant E. coli isolates, it was determined that the E. coli isolate FF21 carried fosfomycin resistance on the plasmid. To ensure the continued effective use of fosfomycin as a treatment option, fosfomycin resistance needs to be detected and closely monitored. Given the global rise in plasmid-transmissible genes, we anticipate a growing resistance to fosfomycin in the near future.

摘要

磷霉素是一种著名的抗生素,对各种细菌病原体具有广谱活性,包括革兰氏阴性菌和一些革兰氏阳性菌,如葡萄球菌。由于已发现该抗生素能有效治疗由多重耐药病原体引起的严重感染,近期对肠外磷霉素的使用进行了修订。磷霉素耐药性的出现可能会威胁到重新使用这种抗生素来治疗细菌感染。在本研究中,共使用了24株从尿液样本中分离出的耐磷霉素大肠杆菌,以调查质粒介导的磷霉素耐药基因的流行情况和分子流行病学。使用基于聚合酶链反应(PCR)的复制起点测定方法,对从分离株中获得的接合质粒和转化质粒的复制起点进行了检测。通过对fosA、fosA3、fosB、fosC、fosC2和fosX基因进行PCR检测以确定磷霉素耐药性,发现24个样本中有1个样本的fosA3基因呈阳性。在3株耐磷霉素大肠杆菌分离株中检测到1类整合子基因,而在任何分离株中均未检测到2类整合子。接合实验表明,fosA3基因在1株同时携带blaTEM、blaCTX-M-15和aac(6')-ib-cr基因的分离株中可转移。通过对转接合子大肠杆菌分离株进行质粒分离,确定大肠杆菌分离株FF21在质粒上携带磷霉素耐药性。为确保磷霉素作为一种治疗选择能持续有效使用,需要检测并密切监测磷霉素耐药性。鉴于全球范围内质粒可传播基因的增加,我们预计在不久的将来对磷霉素的耐药性会不断上升。

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本文引用的文献

1
First Detection of Isolate Co-Harboring Fosfomycin Resistance Gene and ctx-m Among Gram Negative Urine Isolates in a Turkish Hospital.土耳其某医院革兰氏阴性尿液分离株中首次同时检测到磷霉素耐药基因 和 ctx-m。
Microb Drug Resist. 2022 Mar;28(3):317-321. doi: 10.1089/mdr.2021.0114. Epub 2021 Dec 1.
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Mobile fosfomycin resistance genes in Enterobacteriaceae-An increasing threat.肠杆菌科中的移动磷霉素耐药基因——日益严重的威胁。
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New microbiological aspects of fosfomycin.
磷霉素的新微生物学特性
Rev Esp Quimioter. 2019 May;32 Suppl 1(Suppl 1):8-18.
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How is fosfomycin resistance developed in Escherichia coli?大肠杆菌中磷霉素耐药性是如何产生的?
Future Microbiol. 2018 Dec;13:1693-1696. doi: 10.2217/fmb-2018-0294. Epub 2018 Dec 11.
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Resistance to fosfomycin: Mechanisms, Frequency and Clinical Consequences.磷霉素耐药性:机制、频率和临床后果。
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MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.MEGA X:跨越计算平台的分子进化遗传学分析。
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Update on fosfomycin-modified genes in Enterobacteriaceae.肠杆菌科中磷霉素修饰基因的研究进展。
J Microbiol Immunol Infect. 2019 Feb;52(1):9-21. doi: 10.1016/j.jmii.2017.10.006. Epub 2017 Nov 21.
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Urinary Tract Conditions Affect Fosfomycin Activity against Escherichia coli Strains Harboring Chromosomal Mutations Involved in Fosfomycin Uptake.尿路条件影响磷霉素对携带参与磷霉素摄取的染色体突变的大肠杆菌菌株的活性。
Antimicrob Agents Chemother. 2017 Dec 21;62(1). doi: 10.1128/AAC.01899-17. Print 2018 Jan.
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Changing prevalence and antibiotic drug resistance pattern of pathogens seen in community-acquired pediatric urinary tract infections at a tertiary care hospital of North India.印度北部一家三级护理医院社区获得性小儿尿路感染中病原体的流行率变化及抗生素耐药模式
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