Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow Universitygrid.452666.5, Suzhou, Jiangsu, China.
Department of Ophthalmology, The Second Affiliated Hospital of Soochow Universitygrid.452666.5, Suzhou, Jiangsu, China.
mSphere. 2021 Oct 27;6(5):e0077621. doi: 10.1128/mSphere.00776-21. Epub 2021 Oct 13.
Since the discovery of NDM-1 and the worldwide reporting of different variants have raised alarms concerning global health, the problem of carbapenem-resistant (CRE) has become increasingly serious. Therefore, research on the hydrolytic activity and molecular structure of NDM variants is beneficial to the development of antibacterial drugs. NDM has been evolving into variants that possess different hydrolysis activities toward β-lactam antibiotics. Here, we characterized a novel variant, named , identified from a multidrug-resistant Escherichia coli strain from hospital sewage. NDM-33 differed from NDM-5 with a single-amino-acid substitution (A72T). was located in the Tn-related region from an IncX3-type plasmid, pHD6415-NDM, that can be transferred horizontally. The genetic construct of showed higher MICs of carbapenems than a construct. Enzyme kinetics showed that NDM-33 had higher enzymatic activity for meropenem and cefazolin than NDM-5. The emergence of this novel NDM variant could pose a threat to public health because of its transferability and enhanced carbapenem activity. Our study described a novel NDM-33 variant from an E. coli strain isolated from hospital sewage, where it was associated with human disease and antibiotic exposure. Importantly, hospital sewage was increasingly considered to be related to CRE hosts. Pathogens were transmitted from reservoirs through direct and indirect contact, ingestion, and inhalation of contaminated water or aerosols. In addition, under the selective pressure of antibiotics, NDM variants will become the main strain in the hospital water system and evolve into high virulence and high resistance. The monitoring of NDM mutants is of great significance for preventing and controlling the evolution of superbugs.
自 NDM-1 的发现以及不同变体在全球范围内的报道引起了全球健康警报以来,碳青霉烯类耐药(CRE)的问题变得越来越严重。因此,研究 NDM 变体的水解活性和分子结构有助于开发抗菌药物。NDM 已经进化成具有不同β-内酰胺抗生素水解活性的变体。在这里,我们从医院污水中的一株多药耐药大肠杆菌中鉴定了一种新型变体,命名为。NDM-33 与 NDM-5 只有一个氨基酸替换(A72T)不同。位于 IncX3 型质粒 pHD6415-NDM 的 Tn 相关区,可水平转移。的遗传构建体显示出比 更高的碳青霉烯 MIC。酶动力学研究表明,NDM-33 对美罗培南和头孢唑林的酶活性高于 NDM-5。这种新型 NDM 变体的出现可能对公共健康构成威胁,因为它具有可转移性和增强的碳青霉烯活性。我们的研究描述了一种从医院污水中分离的大肠杆菌菌株携带的新型 NDM-33 变体,该变体与人类疾病和抗生素暴露有关。重要的是,医院污水越来越被认为与 CRE 宿主有关。病原体通过直接和间接接触、摄入和吸入受污染的水或气溶胶从储存库传播。此外,在抗生素的选择压力下,NDM 变体将成为医院水系统中的主要菌株,并进化为高毒力和高耐药性。监测 NDM 突变体对预防和控制超级细菌的进化具有重要意义。