小柯机器人

美国哈佛医学院Matthew K. Waldor等研究人员合作发现，十一异戊烯磷酸转位酶赋予条件性的微生物适应性。2022年11月30日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员表示，微生物细胞壁对细胞形状的维持和对外部压力的抵抗至关重要。细胞壁的主要结构成分是肽聚糖（PG），一种位于细胞膜外的多肽交联的糖聚合物。PG的生物合成和结构对环境条件的变化（如pH值和盐度）有反应，但对这种适应的机制还不完全了解。PG和其他细胞表面糖聚合物的前体在细胞质中合成，然后与可回收的脂质载体十一异戊烯磷酸（C55-P）结合，并穿过细胞膜。使C55-P返回到细胞膜细胞质面的转运蛋白一直难以捉摸。

研究人员确定了含有DUF368和DedA跨膜蛋白家族作为候选的C55-P转位酶，填补了微生物细胞表面聚合物的生物生成所需蛋白质的一个重要空白。缺乏同源的含DUF368蛋白的革兰氏阴性和阳性细菌表现出依赖碱性的细胞壁和生存能力缺陷，同时细胞表面C55-P水平增加。含DUF368蛋白和DedA家族成员之间依赖pH值的合成遗传相互作用表明，C55-P转运体的使用是动态的，并受环境输入的调节。霍乱病原体需要C55-P转运体的活性来维持肠道内的生长和细胞形状。研究人员提出，条件性的转运体依赖性提供了脂质载体循环的弹性，并增强了微生物在宿主内外的生存能力。

附：英文原文

Title: Undecaprenyl phosphate translocases confer conditional microbial fitness

Author: Sit, Brandon, Srisuknimit, Veerasak, Bueno, Emilio, Zingl, Franz G., Hullahalli, Karthik, Cava, Felipe, Waldor, Matthew K.

Issue&Volume: 2022-11-30

Abstract: The microbial cell wall is essential for cell shape maintenance and resistance to external stressors1. The primary structural component of the cell wall is peptidoglycan (PG), a glycopolymer with peptide crosslinks located outside of the cell membrane1. PG biosynthesis and structure are responsive to shifting environmental conditions such as pH and salinity2–6, but mechanisms underlying such adaptations are incompletely understood. Precursors of PG and other cell surface glycopolymers are synthesized in the cytoplasm and then delivered across the cell membrane bound to the recyclable lipid carrier undecaprenyl phosphate (C55-P)7. The transporter protein(s) that return C55-P to the cytoplasmic face of the cell membrane have been elusive. Here, we identify the DUF368-containing and DedA transmembrane protein families as candidate C55-P translocases, filling a critical gap in knowledge of the proteins required for the biogenesis of microbial cell surface polymers. Gram-negative and -positive bacteria lacking their cognate DUF368-containing protein exhibited alkaline-dependent cell wall and viability defects, along with increased cell surface C55-P levels. pH-dependent synthetic genetic interactions between DUF368-containing proteins and DedA family members suggest that C55-P transporter usage is dynamic and modulated by environmental inputs. C55-P transporter activity was required by the cholera pathogen for growth and cell shape maintenance in the intestine. We propose that conditional transporter reliance provides resilience in lipid carrier recycling, bolstering microbial fitness within and outside of the host.

DOI: 10.1038/s41586-022-05569-1

Source: https://www.nature.com/articles/s41586-022-05569-1

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
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