研究人员表示，革兰氏阴性菌用肽聚糖（PG）细胞壁和外膜（OM）包围其细胞质膜，外膜由脂多糖（LPS）组成。这种复杂的包膜为药物进入提供了巨大的障碍，并且是决定这些生物体内在抗生素耐药性的一个主要因素。构建该表面的生物生成途径也是许多最有效的抗菌疗法的靶标。因此，了解革兰氏阴性菌包膜组装的分子机制有望帮助开发新的治疗方法，有效解决日益严重的耐药感染问题。虽然PG和OM的合成和组装的个别途径已被很好地描述，但对这些重要的表面层的生物生成是如何协调的几乎一无所知。
研究人员报告了在革兰氏阴性病原体铜绿假单胞菌的PG和LPS合成途径的确立酶之间发现了一种调节作用。结果表明，PG合成酶MurA与LPS合成酶LpxC有直接和特殊的相互作用。此外，MurA被证明能刺激LpxC在细胞和纯化系统中的活性。这些结果支持一个模型，即在许多蛋白细菌物种中，PG和OM层的组装是通过连接其各自合成途径中的确立酶的活性来协调的。
附：英文原文
Title: Coordination of bacterial cell wall and outer membrane biosynthesis
Author: Hummels, Katherine R., Berry, Samuel P., Li, Zhaoqi, Taguchi, Atsushi, Min, Joseph K., Walker, Suzanne, Marks, Debora S., Bernhardt, Thomas G.
Issue&Volume: 2023-03-01
Abstract: Gram-negative bacteria surround their cytoplasmic membrane with a peptidoglycan (PG) cell wall and an outer membrane (OM) with an outer leaflet composed of lipopolysaccharide (LPS)1. This complex envelope presents a formidable barrier to drug entry and is a major determinant of the intrinsic antibiotic resistance of these organisms2. The biogenesis pathways that build the surface are also targets of many of our most effective antibacterial therapies3. Understanding the molecular mechanisms underlying the assembly of the Gram-negative envelope therefore promises to aid the development of new treatments effective against the growing problem of drug-resistant infections. Although the individual pathways for PG and OM synthesis and assembly are well characterized, almost nothing is known about how the biogenesis of these essential surface layers is coordinated. Here we report the discovery of a regulatory interaction between the committed enzymes for the PG and LPS synthesis pathways in the Gram-negative pathogen Pseudomonas aeruginosa. We show that the PG synthesis enzyme MurA interacts directly and specifically with the LPS synthesis enzyme LpxC. Moreover, MurA was shown to stimulate LpxC activity in cells and in a purified system. Our results support a model in which the assembly of the PG and OM layers in many proteobacterial species is coordinated by linking the activities of the committed enzymes in their respective synthesis pathways.
DOI: 10.1038/s41586-023-05750-0
Source: https://www.nature.com/articles/s41586-023-05750-0
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
