Localizing peptidoglycan synthesis for bacterial growth and morphogenesis


Event Date: 

Tue, March 7, 2017






Yves Brun, Ph.D.


Dr Sam Miller

The diversity of shapes of organisms is one of the most fascinating aspects in the field of biology. While bacteria display a myriad of morphologies, the mechanisms that control morphogenesis and the evolution of bacterial morphology are not well understood. One mechanism that drives morphogenesis is the synthesis of peptidoglycan (PG) at specific subcellular sites, or zones. For example, zonal PG synthesis drives the formation of appendage-like extensions of the cell envelope called stalks at distinct sub-cellular positions in alphaproteobacteria, polar in the genus Caulobacter, subpolar in Asticcacaulis excentricus, and bilateral in Asticcacaulis biprosthecum. The SpmX developmental regulator of C. crescentus acquired a new function to drive stalk PG synthesis at subpolar and bi-lateral sites in the Asticcacaulis genus (1). Time-lapse microscopy analysis shows that SpmX initially localizes to a subpolar position in both A. biprosthecum and A. excentricus, where it remains static. Cell elongation in A. excentricus occurs mostly from the septum, and SpmX localization remains subpolar where it drives stalk synthesis. In stark contrast, A. biprosthecum cells elongate from the pole where SpmX is localized, ultimately yielding a cell where SpmX is localized laterally. Most alphaproteobacteria elongate polarly (2), whereas C. crescentus elongates mostly from the septum (3). Fluorescent D-amino acid labeling of areas of PG synthesis (4) in four genera of the Caulobacterales indicated that polar elongation was lost in this group, but reappeared in the more recently evolved A. biprosthecum. We hypothesize that it is the reappearance of a lost ancestral polar growth mode, rather than the targeting of SpmX to a new site, that led to the evolution of lateral stalk synthesis in A. biprosthecum. I will also summarize our recent use of FDAAs to directly analyze the spatio-temporal dynamics of peptidoglycan synthesis at the site of cell division in Bacillus subtilis and its correlation with the activity and dynamics of cytoskeletal and peptidoglycan synthesis proteins, revealing key aspects of their coordination. These studies have for the first time determined the connection between cytoskeletal proteins, peptidoglycan synthesis enzymes, and spatiotemporal patterns of peptidoglycan synthesis at the cell division site, revealing a key role for FtsZ treadmilling in guiding the progressive insertion of new cell wall, building increasingly smaller concentric rings of peptidoglycan to divide the cell (5).



1. Jiang, C., P.J.B. Brown, A. Ducret, and Y.V. Brun. 2014. Sequential evolution of bacterial morphology by co-option of a developmental regulator. Nature, 506, 489-93.

2. Brown, P.J.B., M.A. de Pedro, D.T. Kysela, C. Van der Henst, J. Kim, X. De Bolle, C. Fuqua, and Y.V. Brun. 2012. Polar growth in the Alphaproteobacterial Order Rhizobiales. PNAS, 109: 1697-1701.

3. Aaron, M., Charbon, G., Lam, H., Schwarz, H., Vollmer, W., Jacobs-Wagner, C. 2007. The tubulin homologue FtsZ contributes to cell elongation by guiding cell wall precursor synthesis in Caulobacter crescentus. Molecular Microbiology, 64: 938-52.

4. Kuru, E., H.V. Hughes, P.J.B. Brown, E. Hall, S. Tekkam, F. Cava, M.A. de Pedro, Y.V. Brun, and M.S. VanNieuwenhze. 2012. In situ Probing of Newly Synthesized Peptidoglycan in Live Bacteria with Fluorescent D-Amino Acids. Angewandte Chemie, 51(50):12519-23.

5. Alexandre W. Bisson Filho*, Yen-Pang Hsu*, Georgia R. Squyres*, Erkin Kuru*, Fabai Wu, Calum Jukes, Cees Dekker#, Seamus Holden#, Michael S. VanNieuwenhze#, Yves V. Brun#, and Ethan C. Garner#. Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science, http://dx.doi.org/10.1126/science.aak9973. * co-first authors, #co-corresponding authors.