期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：31
页码：E3243-E3251
DOI：10.1073/pnas.1402158111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThe tropomyosin-like protein, DivIVA, determines the site of growth and cell morphology in mycobacteria. Surprisingly, although DivIVA is located at the tip of the growing cell pole, cell wall addition is excluded from this site. Both late cell wall synthetic enzymes and new cell wall deposition occur at a subpolar space, distinct from the DivIVA-marked cell tip. Instead of directly recruiting terminal cell wall synthetic systems, DivIVA interacts with enzymes involved in the early steps of the cell wall precursor synthesis. These results suggest a unique organization of the polar elongasome, where cell wall precursors are concentrated at the cell tip by DivIVA and then incorporated into the nascent cell wall in an annular pattern at the subpolar zone. Mycobacteria are surrounded by a complex multilayered envelope and elongate at the poles. The principles that organize the coordinated addition of chemically diverse cell wall layers during polar extension remain unclear. We show that enzymes mediating the terminal cytosolic steps of peptidoglycan, arabinogalactan, and mycolic acid synthesis colocalize at sites of cell growth or division. The tropomyosin-like protein, DivIVA, is targeted to the negative curvature of the pole, is enriched at the growing end, and determines cell shape from this site. In contrast, cell wall synthetic complexes are concentrated at a distinct subpolar location. When viewed at subdiffraction resolution, new peptidoglycan is deposited at this subpolar site, and inert cell wall covers the DivIVA-marked tip. The differentiation between polar tip and cell wall synthetic complexes is also apparent at the biochemical level. Enzymes that generate mycolate precursors interact with DivIVA, but the final condensation of mycolic acids occurs in a distinct protein complex at the site of nascent cell wall addition. We propose an ultrastructural model of mycobacterial polar growth where new cell wall is added in an annular zone below the cell tip. This model may be broadly applicable to other bacterial and fungal organisms that grow via polar extension.
