Distinct Spatiotemporal Dynamics of Peptidoglycan Synthesis between Mycobacterium smegmatis and Mycobacterium tuberculosis.
Distinct Spatiotemporal Dynamics of Peptidoglycan Synthesis between Mycobacterium smegmatis and Mycobacterium tuberculosis.
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DOI：
10.1128/mbio.01183-17
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发表时间：
2017-09-12
期刊：
影响因子：
6.4
通讯作者：
Vaubourgeix J
中科院分区：
文献类型：
--
作者：
Botella H;Yang G;Ouerfelli O;Ehrt S;Nathan CF;Vaubourgeix J
肽聚糖（PG）是一种由含有 d-氨基酸的肽交联的聚合物，是细菌细胞壁的重要组成部分。我们发现，荧光 d-丙氨酸类似物 (FDAA) 主要在耻垢分枝杆菌的两个极之一处掺入，但在结核分枝杆菌中，极性优势随着细胞周期的变化而变化：在胞质分裂后，FDAA 主要在两个极之一处掺入，但在胞质分裂之前，FDAA 在两个极处的掺入量相当。这些观察结果表明，分枝杆菌 PG 合成酶位于极和隔膜的功能区室中，并且 PG 合成能力在结核分枝杆菌的新极处成熟。对分枝杆菌 PG 合成生物学的深入了解可能有助于发现能够禁用该过程中以前未被重视的步骤的药物。由于对以前可以治疗细菌感染（包括结核病）的药物的抗菌素耐药性上升，世界各地的人们正在死亡。在这里，我们使用掺入肽聚糖 (PG) 的荧光 d-丙氨酸类似物 (FDAAs)（肽聚糖的合成是一个有吸引力的药物靶点）结合高分辨率和超分辨率显微镜来研究耻垢分枝杆菌和结核分枝杆菌中 PG 合成的时空动态。 FDAA 掺入在耻垢分枝杆菌的两个极之一中占主导地位。相比之下，虽然 FDAA 掺入结核分枝杆菌也是极性的，但作为细胞周期的函数，极性优势存在显着变化。这表明参与 PG 合成的酶位于分枝杆菌的功能区室中，并且结核分枝杆菌拥有在新极处使 PG 合成能力成熟的机制。这可能有助于发现能够削弱这一过程中以前未被重视的步骤的药物。
Peptidoglycan (PG), a polymer cross-linked by d-amino acid-containing peptides, is an essential component of the bacterial cell wall. We found that a fluorescent d-alanine analog (FDAA) incorporates chiefly at one of the two poles in Mycobacterium smegmatis but that polar dominance varies as a function of the cell cycle in Mycobacterium tuberculosis: immediately after cytokinesis, FDAAs are incorporated chiefly at one of the two poles, but just before cytokinesis, FDAAs are incorporated comparably at both. These observations suggest that mycobacterial PG-synthesizing enzymes are localized in functional compartments at the poles and septum and that the capacity for PG synthesis matures at the new pole in M. tuberculosis. Deeper knowledge of the biology of mycobacterial PG synthesis may help in discovering drugs that disable previously unappreciated steps in the process. People are dying all over the world because of the rise of antimicrobial resistance to medicines that could previously treat bacterial infections, including tuberculosis. Here, we used fluorescent d-alanine analogs (FDAAs) that incorporate into peptidoglycan (PG)—the synthesis of which is an attractive drug target—combined with high- and super-resolution microscopy to investigate the spatiotemporal dynamics of PG synthesis in M. smegmatis and M. tuberculosis. FDAA incorporation predominates at one of the two poles in M. smegmatis. In contrast, while FDAA incorporation into M. tuberculosis is also polar, there are striking variations in polar dominance as a function of the cell cycle. This suggests that enzymes involved in PG synthesis are localized in functional compartments in mycobacteria and that M. tuberculosis possesses a mechanism for maturation of the capacity for PG synthesis at the new pole. This may help in discovering drugs that cripple previously unappreciated steps in the process.