Institute for Food Safety and Hygiene, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Microbiologyopen. 2020 Dec;9(12):e1135. doi: 10.1002/mbo3.1135. Epub 2020 Oct 30.
Antimicrobial resistance is one of the major threats to the health and welfare of both humans and animals. The shortage of new antimicrobial agents has led to the re-evaluation of old antibiotics such as fosfomycin as a potential regimen for treating multidrug-resistant bacteria especially extended-spectrum-beta-lactamase- and carbapenemase-producing Enterobacteriaceae. Fosfomycin is a broad-spectrum bactericidal antibiotic that inhibits the initial step of the cell wall biosynthesis. Fosfomycin resistance can occur due to mutation in the drug uptake system or by the acquisition of fosfomycin-modifying enzymes. In this review, we focus on mobile fosfomycin-resistant genes encoding glutathione-S-transferase which are mainly responsible for fosfomycin resistance in Enterobacteriaceae, that is, fosA and its subtypes, fosC2, and the recently described fosL1-L2. We summarized the proposed origins of the different resistance determinants and highlighted the different plasmid types which are attributed to the dissemination of fosfomycin-modifying enzymes. Thereby, IncF and IncN plasmids play a predominant role. The detection of mobile fosfomycin-resistant genes in Enterobacteriaceae has increased in recent years. Similar to the situation in (East) Asia, the most frequently detected fosfomycin-resistant gene in Europe is fosA3. Mobile fosfomycin-resistant genes have been detected in isolates of human, animal, food, and environmental origin which leads to a growing concern regarding the risk of spread of such bacteria, especially Escherichia coli and Salmonella, at the human-animal-environment interface.
抗微生物药物耐药性是人类和动物健康和福利的主要威胁之一。新型抗菌药物的短缺导致人们重新评估旧抗生素，如磷霉素，将其作为治疗多药耐药细菌（尤其是产超广谱β-内酰胺酶和碳青霉烯酶的肠杆菌科细菌）的潜在方案。磷霉素是一种广谱杀菌抗生素，可抑制细胞壁生物合成的初始步骤。磷霉素耐药性可能由于药物摄取系统的突变或获得磷霉素修饰酶而发生。在这篇综述中，我们重点介绍了编码谷胱甘肽-S-转移酶的可移动磷霉素耐药基因，这些基因主要负责肠杆菌科中的磷霉素耐药性，即 fosA 及其亚型 fosC2，以及最近描述的 fosL1-L2。我们总结了不同耐药决定因素的可能起源，并强调了不同的质粒类型，这些类型归因于磷霉素修饰酶的传播。因此，IncF 和 IncN 质粒起着主要作用。近年来，肠杆菌科中可移动磷霉素耐药基因的检测有所增加。与东亚的情况类似，欧洲最常检测到的磷霉素耐药基因是 fosA3。在人类、动物、食品和环境来源的分离物中已经检测到了可移动的磷霉素耐药基因，这导致人们越来越担心这种细菌（尤其是大肠杆菌和沙门氏菌）在人类-动物-环境界面传播的风险。
