Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, Key Laboratory for Chemical Biology of Fujian Province State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
ACS Chem Biol. 2021 Jul 16;16(7):1164-1171. doi: 10.1021/acschembio.1c00346. Epub 2021 Jun 29.
By catalyzing a 3-3 cross-link in peptidoglycan, l,d-transpeptidases (Ldts) can cause resistance to β-lactams in some pathogens . However, the prevalence of Ldt and Ldt-mediated responses to different β-lactams have never been explored. Here, we apply an metabolic labeling strategy to study their biodistributions and Ldt-induced bacterial responses to β-lactams in the mouse gut microbiota. A tetrapeptide-based fluorescent probe that functions as a substrate for Ldts in Gram-positive bacteria efficiently labels ∼18% of total gut bacteria after gavage, suggesting Ldts' high prevalence in gut microbiota. The cellular distributions of 3-3 cross-links on three gut bacterial species were then identified with the aid of fluorescence hybridization to identify the bacterial taxa. After oral administration of two β-lactams, ampicillin and meropenem, only the latter efficiently inhibits the tetrapeptide labeling, suggesting that Ldts may be able to cause resistance to some β-lactams in the mammalian gut.
通过催化肽聚糖中的 3-3 交联，L，d-转肽酶（Ldts）可导致某些病原体对β-内酰胺类抗生素产生耐药性。然而，Ldt 的流行程度以及对不同β-内酰胺类抗生素的 Ldt 介导反应从未被探索过。在这里，我们应用代谢标记策略来研究它们在小鼠肠道微生物群中的生物分布和 Ldt 诱导的细菌对β-内酰胺类抗生素的反应。一种基于四肽的荧光探针，在革兰氏阳性菌中作为 Ldts 的底物，在灌胃后有效地标记了约 18%的总肠道细菌，这表明 Ldts 在肠道微生物群中具有很高的流行率。然后，借助荧光杂交技术，确定了三种肠道细菌物种中 3-3 交联的细胞分布，以鉴定细菌分类群。在口服两种β-内酰胺类抗生素氨苄西林和美罗培南后，只有后者能有效地抑制四肽的标记，这表明 Ldt 可能导致哺乳动物肠道中某些β-内酰胺类抗生素的耐药性。
