Interaction and modulation of two antagonistic cell wall enzymes of mycobacteria.
Interaction and modulation of two antagonistic cell wall enzymes of mycobacteria.
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DOI：
10.1371/journal.ppat.1001020
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发表时间：
2010-07-29
期刊：
影响因子：
6.7
通讯作者：
Rubin EJ
中科院分区：
文献类型：
--
作者：
Hett EC;Chao MC;Rubin EJ
Bacterial cell growth and division require coordinated cell wall hydrolysis and synthesis, allowing for the removal and expansion of cell wall material. Without proper coordination, unchecked hydrolysis can result in cell lysis. How these opposing activities are simultaneously regulated is poorly understood. In Mycobacterium tuberculosis, the resuscitation-promoting factor B (RpfB), a lytic transglycosylase, interacts and synergizes with Rpf-interacting protein A (RipA), an endopeptidase, to hydrolyze peptidoglycan. However, it remains unclear what governs this synergy and how it is coordinated with cell wall synthesis. Here we identify the bifunctional peptidoglycan-synthesizing enzyme, penicillin binding protein 1 (PBP1), as a RipA-interacting protein. PBP1, like RipA, localizes both at the poles and septa of dividing cells. Depletion of the ponA1 gene, encoding PBP1 in M. smegmatis, results in a severe growth defect and abnormally shaped cells, indicating that PBP1 is necessary for viability and cell wall stability. Finally, PBP1 inhibits the synergistic hydrolysis of peptidoglycan by the RipA-RpfB complex in vitro. These data reveal a post-translational mechanism for regulating cell wall hydrolysis and synthesis through protein–protein interactions between enzymes with antagonistic functions. Bacteria have a complex problem to solve. On one hand, they need to hydrolyze existing and synthesize new cell wall to allow for cell expansion during growth. On the other hand, they need to maintain a continuous layer of cell wall to preserve shape and protect from osmotic lysis. To do this, bacteria must tightly coordinate the processes of cell wall hydrolysis and synthesis. How these opposing activities are simultaneously regulated is poorly understood. We previously demonstrated the interaction between two cell wall hydrolytic proteins, RpfB and RipA, in mycobacteria. This RpfB-RipA complex resulted in enhanced hydrolysis of cell wall, suggesting protein–protein interactions as one mechanism for regulating hydrolysis. However, what regulates interactions of these potentially lethal enzymes and what coordinates hydrolysis with synthesis remains unknown. To investigate this question, we screened for mycobacterial proteins that interact with, and thus potentially regulate, RipA. Here, we report the interaction of RipA with PBP1, a cell-wall-synthesizing enzyme. Depletion of PBP1 from mycobacteria results in misshapen cells and impaired growth. Moreover, we find that PBP1 inhibits the synergistic activity of the RipA-RpfB interaction. These data reveal a mechanism for coordinating cell wall hydrolysis and synthesis through interactions between antagonistic enzymes.
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