Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.
J Antimicrob Chemother. 2021 Mar 12;76(4):836-864. doi: 10.1093/jac/dkaa513.
Class D β-lactamases are composed of 14 families and the majority of the member enzymes are included in the OXA family. The genes for class D β-lactamases are frequently identified in the chromosome as an intrinsic resistance determinant in environmental bacteria and a few of these are found in mobile genetic elements carried by clinically significant pathogens. The most dominant OXA family among class D β-lactamases is superheterogeneous and the family needs to have an updated scheme for grouping OXA subfamilies through phylogenetic analysis. The OXA enzymes, even the members within a subfamily, have a diverse spectrum of resistance. Such varied activity could be derived from their active sites, which are distinct from those of the other serine β-lactamases. Their substrate profile is determined according to the size and position of the P-, Ω- and β5-β6 loops, assembling the active-site channel, which is very hydrophobic. Also, amino acid substitutions occurring in critical structures may alter the range of hydrolysed substrates and one subfamily could include members belonging to several functional groups. This review aims to describe the current class D β-lactamases including the functional groups, occurrence types (intrinsic or acquired) and substrate spectra and, focusing on the major OXA family, a new model for subfamily grouping will be presented.
D 类β-内酰胺酶由 14 个家族组成，大多数成员酶都包含在 OXA 家族中。D 类β-内酰胺酶的基因通常在染色体上作为环境细菌的固有耐药决定因素被识别，其中少数存在于临床重要病原体携带的移动遗传元件中。D 类β-内酰胺酶中最主要的 OXA 家族是超级异质的，需要通过系统发育分析对 OXA 亚家族进行分组的更新方案。OXA 酶，即使是亚家族中的成员，也具有多样化的耐药谱。这种不同的活性可能源于它们的活性位点，与其他丝氨酸β-内酰胺酶的活性位点不同。它们的底物谱取决于 P-、Ω-和β5-β6 环的大小和位置，组装活性位点通道，该通道非常疏水。此外，发生在关键结构中的氨基酸取代可能会改变被水解的底物范围，一个亚家族可能包括属于几个功能组的成员。本综述旨在描述当前的 D 类β-内酰胺酶，包括功能组、发生类型（固有或获得）和底物谱，并重点介绍主要的 OXA 家族，提出一个新的亚家族分组模型。
