Bonnin Rémy A, Jousset Agnès B, Emeraud Cécile, Oueslati Saoussen, Dortet Laurent, Naas Thierry
Team "Resist" UMR1184 "Immunology of Viral, Auto-Immune, Hematological and Bacterial diseases (IMVA-HB)," INSERM, Université Paris-Saclay, CEA, LabEx LERMIT, Faculty of Medicine, Le Kremlin-Bicêtre, France.
Associated French National Reference Center for Antibiotic Resistance: Carbapenemase-Producing Enterobacteriaceae, Le Kremlin-Bicêtre, France.
Front Med (Lausanne). 2021 Jan 20;7:616490. doi: 10.3389/fmed.2020.616490. eCollection 2020.
Gram-negative bacteria, especially Enterobacterales, have emerged as major players in antimicrobial resistance worldwide. Resistance may affect all major classes of anti-gram-negative agents, becoming multidrug resistant or even pan-drug resistant. Currently, β-lactamase-mediated resistance does not spare even the most powerful β-lactams (carbapenems), whose activity is challenged by carbapenemases. The dissemination of carbapenemases-encoding genes among Enterobacterales is a matter of concern, given the importance of carbapenems to treat nosocomial infections. Based on their amino acid sequences, carbapenemases are grouped into three major classes. Classes A and D use an active-site serine to catalyze hydrolysis, while class B (MBLs) require one or two zinc ions for their activity. The most important and clinically relevant carbapenemases are KPC, IMP/VIM/NDM, and OXA-48. However, several carbapenemases belonging to the different classes are less frequently detected. They correspond to class A (SME-, Nmc-A/IMI-, SFC-, GES-, BIC-like…), to class B (GIM, TMB, LMB…), class C (CMY-10 and ACT-28), and to class D (OXA-372). This review will address the genetic diversity, biochemical properties, and detection methods of minor acquired carbapenemases in Enterobacterales.
革兰氏阴性菌,尤其是肠杆菌科细菌,已成为全球抗菌药物耐药性的主要参与者。耐药性可能影响所有主要类别的抗革兰氏阴性菌药物,导致多重耐药甚至泛耐药。目前,β-内酰胺酶介导的耐药性甚至连最强大的β-内酰胺类药物(碳青霉烯类)也无法幸免,其活性受到碳青霉烯酶的挑战。鉴于碳青霉烯类药物在治疗医院感染中的重要性,肠杆菌科细菌中碳青霉烯酶编码基因的传播令人担忧。根据其氨基酸序列,碳青霉烯酶可分为三大类。A类和D类利用活性位点丝氨酸催化水解,而B类(金属β-内酰胺酶)的活性需要一个或两个锌离子。最重要且与临床相关的碳青霉烯酶是KPC、IMP/VIM/NDM和OXA-48。然而,属于不同类别的几种碳青霉烯酶较少被检测到。它们分别对应于A类(SME-、Nmc-A/IMI-、SFC-、GES-、BIC样……)、B类(GIM、TMB、LMB……)、C类(CMY-10和ACT-28)以及D类(OXA-372)。本综述将探讨肠杆菌科细菌中少见的获得性碳青霉烯酶的遗传多样性、生化特性及检测方法。