Abstract
The peptidoglycan cell wall is essential for the survival and morphogenesis of bacteria1. For decades, it was thought that only class A penicillin-binding proteins (PBPs) and related enzymes effected peptidoglycan synthesis. Recently, it was shown that RodA—a member of the unrelated SEDS protein family—also acts as a peptidoglycan polymerase2,3,4. Not all bacteria require RodA for growth; however, its homologue, FtsW, is a core member of the divisome complex that appears to be universally essential for septal cell wall assembly5,6. FtsW was previously proposed to translocate the peptidoglycan precursor lipid II across the cytoplasmic membrane7,8. Here, we report that purified FtsW polymerizes lipid II into peptidoglycan, but show that its polymerase activity requires complex formation with its partner class B PBP. We further demonstrate that the polymerase activity of FtsW is required for its function in vivo. Thus, our findings establish FtsW as a peptidoglycan polymerase that works with its cognate class B PBP to produce septal peptidoglycan during cell division.
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Data availability
All data generated or analysed during this study are available from the corresponding authors upon request.
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Acknowledgements
We thank the Microscopy Resources on the North Quad core at the Harvard Medical School for help with imaging and analysis. LC-MS data were acquired on an Agilent 6520 Q-TOF mass spectrometer supported by the Taplin Funds for Discovery Program. Funding for this work was provided by National Institutes of Health grants R01 AI083365 (to T.G.B.), R01 AI099144 (to T.G.B. and S.W.), R01 GM076710 (to D.K. and S.W.), CETR U19 AI109764 (to A.C.K., D.K., T.G.B. and S.W.) and F32 GM123579 (to M.A.W.). A.T. is supported in part by the Funai Overseas Scholarship. W.L. is supported in part by the Charles A. King Trust Postdoctoral Research Fellowship Program.
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A.T., T.G.B. and S.W. conceived the project. A.T., D.K., T.G.B. and S.W. designed and coordinated the overall study. The experiments were performed by A.T., M.A.W., L.S.M. and W.L. M.S. and A.C.K performed the bioinformatics analysis and provided advice on protein preparation. The manuscript was written by A.T., M.A.W., T.G.B. and S.W., with input from all authors.
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Taguchi, A., Welsh, M.A., Marmont, L.S. et al. FtsW is a peptidoglycan polymerase that is functional only in complex with its cognate penicillin-binding protein. Nat Microbiol 4, 587–594 (2019). https://doi.org/10.1038/s41564-018-0345-x
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DOI: https://doi.org/10.1038/s41564-018-0345-x
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