水解碳青霉烯类OXA型β-内酰胺酶的研究进展

Advances in carbapenem-hydrolyzing OXA-type β-lactamases

摘要:

苯唑西林酶(OXA酶)属于D类β-内酰胺酶, 因其对苯唑西林具有较高的水解活性而得名。OXA型β-内酰胺酶定位于染色体或质粒, 并由质粒、转座子等可移动元件介导其在菌株间的水平转移, 现已衍生出一千余种变体。近年来, 水解碳青霉烯类药物的OXA酶出现并在菌株间传播, 给临床抗感染治疗带来巨大挑战。2001年土耳其从1株肺炎克雷伯菌中发现了OXA-48酶, 这是在肠杆菌目菌株中第一次发现可水解碳青霉烯类药物的OXA酶。随后, 又发现了OXA-48酶多种变体, 统称为OXA-48-like酶, 其不仅水解青霉素类药物能力强, 还可以水解厄他培南、美罗培南等碳青霉烯类药物, 介导对包括碳青霉烯类在内的多种β-内酰胺类药物耐药。希瓦氏菌被认为是bla_OXA-48-like基因的起源, 现已报道12个起源于希瓦氏菌的OXA-48-like。为全面掌握可水解碳青霉烯类OXA酶的特征和分布, 本文就水解碳青霉烯类药物的OXA酶的来源、分布现状、流行特点及发展趋势进行综述。

Abstract:

Oxacillinase (OXA) belongs to class D β-lactamase, named for its high hydrolytic activity on oxacillin. OXA-type β-lactamases locate on chromosomes or plasmids, and their horizontal transfer among strains is mediated by mobile elements such as plasmids and transposons. Over a thousand variants have been derived to date. In recent years, carbapenem-hydrolyzing OXA have emerged and spread among strains, posing a huge challenge to clinical anti-infection treatment. In 2001, OXA-48 was found in a strain of Klebsiella pneumoniae in Turkey, which was the firstly reported carbapenem-hydrolyzing OXA in Enterobacterales. Subsequently, various variants of OXA-48 enzyme were identified and nominated as OXA-48-like enzymes. These enzymes not only have strong hydrolytic activity against penicillin, but also hydrolyze carbapenems such as ertapenem and meropenem, mediating resistance to various β-lactam antimicrobial agents, including carbapenems. Shewanella spp. is considered to be the origin of the bla_OXA-48-like gene, and 12 OXA-48-like genes derived from Shewanella spp. have been reported. In order to comprehensively understand the characteristics and distribution of carbapenem-hydrolyzing OXA enzymes, this article reviews the origin, distribution status, epidemiological characteristics, and development trends of carbapenem-hydrolyzing OXA.