Department of Chemistry and Biochemistry, McCourtney Hall , University of Notre Dame , Notre Dame , Indiana 46556 , United States.
Chem Rev. 2018 Jun 27;118(12):5952-5984. doi: 10.1021/acs.chemrev.8b00277. Epub 2018 May 30.
The importance of the cell wall to the viability of the bacterium is underscored by the breadth of antibiotic structures that act by blocking key enzymes that are tasked with cell-wall creation, preservation, and regulation. The interplay between cell-wall integrity, and the summoning forth of resistance mechanisms to deactivate cell-wall-targeting antibiotics, involves exquisite orchestration among cell-wall synthesis and remodeling and the detection of and response to the antibiotics through modulation of gene regulation by specific effectors. Given the profound importance of antibiotics to the practice of medicine, the assertion that understanding this interplay is among the most fundamentally important questions in bacterial physiology is credible. The enigmatic regulation of the expression of the AmpC β-lactamase, a clinically significant and highly regulated resistance response of certain Gram-negative bacteria to the β-lactam antibiotics, is the exemplar of this challenge. This review gives a current perspective to this compelling, and still not fully solved, 35-year enigma.
细胞壁对细菌活力的重要性,突出体现在抗生素结构的多样性上,这些抗生素通过阻断负责细胞壁合成、维持和调节的关键酶来发挥作用。细胞壁完整性与抵抗机制的相互作用,以失活针对细胞壁的抗生素,涉及到细胞壁合成和重塑之间的精细协调,以及通过特定效应物调节基因调控来检测和响应抗生素。鉴于抗生素对医学实践的深远重要性,断言理解这种相互作用是细菌生理学中最重要的问题之一是可信的。ampCβ-内酰胺酶表达的神秘调节就是这一挑战的范例,ampCβ-内酰胺酶是某些革兰氏阴性菌对β-内酰胺类抗生素具有临床意义和高度调节的耐药反应的重要表现。这篇综述为这个引人入胜且尚未完全解决的 35 年之谜提供了当前的视角。