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[241株临床分离株中苯唑西林酶的基因多样性分析]

[Genetic diversity analysis of oxacillinase in 241 clinical isolates of ].

作者信息

Li Y L, Zhang J Y, Fu Y B, Sun M Q, Miao B B, Gong X Y, Han X, Xing H, Gao P F, Li J C, Tang Y T, Fan X Y, Ge Y L, Zhou H J, Li J, Dong A Y

机构信息

Affiliated Hospital of North China University of Science and Technology, Tangshan 063000, China.

National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2025 Jul 6;59(7):1004-1012. doi: 10.3760/cma.j.cn112150-20240920-00756.

Abstract

To analyze the carriage status, subtype distribution and flanking gene sequence characteristics of oxacillinases (OXA enzyme) in 241 clinical strains of Pseudomonas aeruginosa, and assess their roles in the drug resistance of and ability to horizontally transfer across species. Clinical isolates were collected from four hospitals in Sanya, Tangshan, Zhangjiakou, and Beijing. The prevalence of oxacillinases and their flanking gene sequences was analyzed by whole-genome sequencing (NGS) and bioinformatic approaches. A total of 241 isolates of were gathered, and 35 subtypes were identified through screening of 252 genes. These genes were classified into three subfamilies: (241, 95.6%), (9, 3.6%) and (2, 0.8%). Among these, 11 subtypes (11, 31.4%) were novel subtypes. Nine of these belonged to the subfamily and were designated as , , , , , , , , and . The remaining two belonged to the subfamily and were named and . Compared to the amino acid sequence of OXA-10, the newly identified subtype OXA-1247 exhibited a mutation at position 117, where a valine was replaced by a leucine. This change was thought to improve the enzyme's ability to hydrolyze carbapenems. In the analysis of the flanking sequences of the genes, Class I integrons were identified in four bacterial strains. The variable regions of these integrons carried three distinct patterns of resistance gene cassettes: ()(), () and ()-. Among these, the strain BJ2326 carried a class I integron that was connected to the downstream IS element to form a composite class I integron structure, additionally carrying the resistance gene . Out of the 223 non-wild-type strains, 127 strains exhibited non-wild-type profiles to the four beta-lactam antibiotics MEM, CAZ, FEP, and TZP, with the combination of MEM+CAZ+FEP being the most prevalent, representing 57.0% of the total. The genes in 241 clinical strains showed diversity. Some genes had a co-transfer risk with the metallo-β-lactamase resistance gene blaIMP-45. Among the 11 newly discovered subtypes, the new subtype OXA-1247 may have carbapenemase activity and potential for horizontal transfer.

摘要

分析241株铜绿假单胞菌临床菌株中氧青霉烯酶(OXA酶)的携带情况、亚型分布及侧翼基因序列特征,评估其在耐药性及跨物种水平转移能力中的作用。临床分离株来自三亚、唐山、张家口和北京的四家医院。通过全基因组测序(NGS)和生物信息学方法分析氧青霉烯酶及其侧翼基因序列的流行情况。共收集到241株分离株,通过对252个OXA基因进行筛选,鉴定出35种亚型。这些基因分为三个亚家族:OXA-51-like(241株,95.6%)、OXA-23-like(9株,3.6%)和OXA-40-like(2株,0.8%)。其中,11种亚型(11株,31.4%)为新型OXA亚型。其中9种属于OXA-23-like亚家族,分别命名为OXA-1241、OXA-1242、OXA-1243、OXA-1244、OXA-1245、OXA-1246、OXA-1248、OXA-1249和OXA-1250。其余两种属于OXA-40-like亚家族,命名为OXA-1251和OXA-1252。与OXA-10的氨基酸序列相比,新鉴定的亚型OXA-1247在第117位发生突变,缬氨酸被亮氨酸取代。这种变化被认为提高了该酶水解碳青霉烯类药物的能力。在对OXA基因侧翼序列的分析中,在4株细菌中鉴定出I类整合子。这些整合子的可变区携带三种不同模式的耐药基因盒:(aadA2)(dfrA12)、(aadA2)和(aadA2)-tet(A)。其中,菌株BJ2326携带一个与下游IS元件相连形成复合I类整合子结构的I类整合子,还携带耐药基因aac(6')-Ib-cr。在223株非野生型OXA菌株中,127株对四种β-内酰胺类抗生素美罗培南(MEM)、头孢他啶(CAZ)、头孢吡肟(FEP)和哌拉西林/他唑巴坦(TZP)呈现非野生型谱型,其中MEM+CAZ+FEP组合最为常见,占总数的57.0%。241株临床OXA菌株中的OXA基因表现出多样性。一些OXA基因与金属β-内酰胺酶耐药基因blaIMP-45存在共转移风险。在11种新发现的OXA亚型中,新亚型OXA-1247可能具有碳青霉烯酶活性和水平转移潜力。

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