Sassine Jad, Xu Meizhu, Sidiq Karzan R, Emmins Robyn, Errington Jeff, Daniel Richard A
Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4AH, UK.
Mol Microbiol. 2017 Oct;106(2):304-318. doi: 10.1111/mmi.13765. Epub 2017 Aug 29.
Bacterial cell division involves the dynamic assembly of a diverse set of proteins that coordinate the invagination of the cell membrane and synthesis of cell wall material to create the new cell poles of the separated daughter cells. Penicillin-binding protein PBP 2B is a key cell division protein in Bacillus subtilis proposed to have a specific catalytic role in septal wall synthesis. Unexpectedly, we find that a catalytically inactive mutant of PBP 2B supports cell division, but in this background the normally dispensable PBP 3 becomes essential. Phenotypic analysis of pbpC mutants (encoding PBP 3) shows that PBP 2B has a crucial structural role in assembly of the division complex, independent of catalysis, and that its biochemical activity in septum formation can be provided by PBP 3. Bioinformatic analysis revealed a close sequence relationship between PBP 3 and Staphylococcus aureus PBP 2A, which is responsible for methicillin resistance. These findings suggest that mechanisms for rescuing cell division when the biochemical activity of PBP 2B is perturbed evolved prior to the clinical use of β-lactams.
细菌细胞分裂涉及多种蛋白质的动态组装，这些蛋白质协调细胞膜内陷和细胞壁物质合成，以形成分离的子细胞的新细胞极。青霉素结合蛋白PBP 2B是枯草芽孢杆菌中的一种关键细胞分裂蛋白，被认为在隔膜壁合成中具有特定的催化作用。出乎意料的是，我们发现PBP 2B的催化失活突变体支持细胞分裂，但在此背景下，通常可有可无的PBP 3变得必不可少。pbpC突变体（编码PBP 3）的表型分析表明，PBP 2B在分裂复合体的组装中具有关键的结构作用，与催化作用无关，并且其在隔膜形成中的生化活性可由PBP 3提供。生物信息学分析揭示了PBP 3与金黄色葡萄球菌PBP 2A之间密切的序列关系，后者负责耐甲氧西林。这些发现表明，当PBP 2B的生化活性受到干扰时拯救细胞分裂的机制在β-内酰胺临床使用之前就已进化。
