Institut Pasteur, Unité de Biochimie des Interactions Macromoléculaires, Paris, France.
Mol Microbiol. 2012 Jul;85(1):164-78. doi: 10.1111/j.1365-2958.2012.08100.x. Epub 2012 Jun 7.
Chlamydiae are obligate intracellular bacterial pathogens that have extensively reduced their genome in adapting to the intracellular environment. The chlamydial genome contains only three annotated cell division genes and lacks ftsZ. How this obligate intracellular pathogen divides is uncharacterized. Chlamydiae contain two high-molecular-weight (HMW) penicillin binding proteins (Pbp) implicated in peptidoglycan synthesis, Pbp2 and Pbp3/FtsI. We show here, using HMW Pbp-specific penicillin derivatives, that both Pbp2 and Pbp3 are essential for chlamydial cell division. Ultrastructural analyses of antibiotic-treated cultures revealed distinct phenotypes: Pbp2 inhibition induced internal cell bodies within a single outer membrane whereas Pbp3 inhibition induced elongated phenotypes with little internal division. Each HMW Pbp interacts with the Chlamydia cell division protein FtsK. Chlamydiae are coccoid yet contain MreB, a rod shape-determining protein linked to Pbp2 in bacilli. Using MreB-specific antibiotics, we show that MreB is essential for chlamydial growth and division. Importantly, co-treatment with MreB-specific and Pbp-specific antibiotics resulted in the MreB-inhibited phenotype, placing MreB upstream of Pbp function in chlamydial cell division. Finally, we showed that MreB also interacts with FtsK. We propose that, in Chlamydia, MreB acts as a central co-ordinator at the division site to substitute for the lack of FtsZ in this bacterium.
衣原体是专性细胞内细菌病原体，为适应细胞内环境，其基因组大大减少。衣原体基因组仅包含三个注释的细胞分裂基因，且缺乏 ftsZ。这种专性细胞内病原体如何分裂尚不清楚。衣原体包含两个与肽聚糖合成有关的高分子量（HMW）青霉素结合蛋白（Pbp），即 Pbp2 和 Pbp3/FtsI。我们使用 HMW Pbp 特异性青霉素衍生物，证明 Pbp2 和 Pbp3 对衣原体细胞分裂都是必需的。抗生素处理培养物的超微结构分析显示出不同的表型：Pbp2 抑制导致单个外膜内的内部细胞体，而 Pbp3 抑制导致内部分裂很少的伸长表型。每个 HMW Pbp 都与衣原体细胞分裂蛋白 FtsK 相互作用。衣原体呈球菌状，但含有 MreB，这是一种与杆菌中的 Pbp2 相关的杆状决定蛋白。使用 MreB 特异性抗生素，我们证明 MreB 是衣原体生长和分裂所必需的。重要的是，MreB 特异性和 Pbp 特异性抗生素的共同处理导致了 MreB 抑制表型，这表明 MreB 在衣原体细胞分裂中位于 Pbp 功能的上游。最后，我们表明 MreB 还与 FtsK 相互作用。我们提出，在衣原体中，MreB 作为分裂部位的中央协调因子，替代了该细菌中缺乏 FtsZ 的作用。
