State Key Lab of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong.
Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong.
Commun Biol. 2022 May 31;5(1):522. doi: 10.1038/s42003-022-03465-y.
Recently, many TetX variants such as Tet(X3~14) were reported to confer resistance to tigecycline which is a last-resort antibiotic used to treat infections caused by multidrug-resistant bacteria. In this study, we identified essential residues including 329, 339, 340, 350, and 351 in TetX variants that mediated the evolution of the tigecycline-inactive Tet(X2) enzyme to the active forms of Tet(X3) and Tet(X4). Based on their amino acid sequences and functional features, we classified TetX variants into TetX-A class, TetX-B class and TetX-C class. We further found that TetX-A class variants originated from Bacteroidetes, with some variants further evolving to TetX-C class and acquired by Enterobacteriaceae. On the other hand, our data showed that some variants genes belonging to TetX-A class evolved directly to TetX-B class, which was further transmitted to Acinetobacter spp. This new classification system may facilitate better clinical management of patients infected by TetX-producing strains.
最近，许多 TetX 变体（如 Tet(X3~14)）被报道对替加环素具有耐药性，替加环素是一种最后手段的抗生素，用于治疗由多药耐药菌引起的感染。在这项研究中，我们鉴定了 TetX 变体中包括 329、339、340、350 和 351 在内的必需残基，这些残基介导了替加环素非活性 Tet(X2)酶向活性 Tet(X3)和 Tet(X4)形式的进化。根据它们的氨基酸序列和功能特征，我们将 TetX 变体分为 TetX-A 类、TetX-B 类和 TetX-C 类。我们进一步发现，TetX-A 类变体来源于拟杆菌门，其中一些变体进一步进化为 TetX-C 类，并被肠杆菌科获得。另一方面，我们的数据表明，一些属于 TetX-A 类的变体基因直接进化为 TetX-B 类，然后进一步传播到不动杆菌属。这个新的分类系统可能有助于更好地管理感染 TetX 产生菌的患者。
