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      MreB filaments align along greatest principal membrane curvature to orient cell wall synthesis

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          MreB is essential for rod shape in many bacteria. Membrane-associated MreB filaments move around the rod circumference, helping to insert cell wall in the radial direction to reinforce rod shape. To understand how oriented MreB motion arises, we altered the shape of Bacillus subtilis. MreB motion is isotropic in round cells, and orientation is restored when rod shape is externally imposed. Stationary filaments orient within protoplasts, and purified MreB tubulates liposomes in vitro, orienting within tubes. Together, this demonstrates MreB orients along the greatest principal membrane curvature, a conclusion supported with biophysical modeling. We observed that spherical cells regenerate into rods in a local, self-reinforcing manner: rapidly propagating rods emerge from small bulges, exhibiting oriented MreB motion. We propose that the coupling of MreB filament alignment to shape-reinforcing peptidoglycan synthesis creates a locally-acting, self-organizing mechanism allowing the rapid establishment and stable maintenance of emergent rod shape.

          eLife digest

          Many bacteria are surrounded by both a cell membrane and a cell wall – a rigid outer covering made of sugars and short protein chains. The cell wall often determines which of a variety of shapes – such as rods or spheres – the bacteria grow into. One protein required to form the rod shape is called MreB. This protein forms filaments that bind to the bacteria’s cell membrane and associate with the enzymes that build the cell wall. Together, these filament-enzyme complexes rotate around the cell to build and reinforce the cell wall in a hoop-like manner. But how do the MreB filaments know how to move around the circumference of the rod, instead of moving in any other direction?

          Using a technique called total internal reflection microscopy to study how MreB filaments move across bacteria cells, Hussain, Wivagg et al. show that the filaments sense the shape of a bacterium by orienting along the direction of greatest curvature. As a result, the filaments in rod-shaped cells orient and move around the rod, while in spherical bacteria they move in all directions. However, spherical bacteria can regenerate into rods from small surface ‘bulges’. The MreB filaments in the bulges move in an oriented way, helping them to generate the rod shape.

          Hussain, Wivagg et al. also found that forcing cells that lack a cell wall into a rod shape caused the MreB filaments bound to the cell membrane to orient and circle around the rod. This shows that the organization of the filaments is sufficient to shape the cell wall.

          In the future, determining what factors control the activity of the MreB filaments and the enzymes they associate with might reveal new targets for antibiotics that disrupt the cell wall and so kill the bacteria. This will require higher resolution microscopes to be used to examine the cell wall in more detail. The activity of all the proteins involved in building cell walls will also need to be extensively characterized.

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          Most cited references 51

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          In Situ probing of newly synthesized peptidoglycan in live bacteria with fluorescent D-amino acids.

          Tracking a bug's life: Peptidoglycan (PG) of diverse bacteria is labeled by exploiting the tolerance of cells for incorporating different non-natural D-amino acids. These nontoxic D-amino acids preferably label the sites of active PG synthesis, thereby enabling fine spatiotemporal tracking of cell-wall dynamics in phylogenetically and morphologically diverse bacteria. HCC = 7-hydroxycoumarin, NBD = 7-nitrobenzofurazan, TAMRA = carboxytetramethylrhodamine. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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            Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli.

             J. Höltje (1998)
            To withstand the high intracellular pressure, the cell wall of most bacteria is stabilized by a unique cross-linked biopolymer called murein or peptidoglycan. It is made of glycan strands [poly-(GlcNAc-MurNAc)], which are linked by short peptides to form a covalently closed net. Completely surrounding the cell, the murein represents a kind of bacterial exoskeleton known as the murein sacculus. Not only does the sacculus endow bacteria with mechanical stability, but in addition it maintains the specific shape of the cell. Enlargement and division of the murein sacculus is a prerequisite for growth of the bacterium. Two groups of enzymes, hydrolases and synthases, have to cooperate to allow the insertion of new subunits into the murein net. The action of these enzymes must be well coordinated to guarantee growth of the stress-bearing sacculus without risking bacteriolysis. Protein-protein interaction studies suggest that this is accomplished by the formation of a multienzyme complex, a murein-synthesizing machinery combining murein hydrolases and synthases. Enlargement of both the multilayered murein of gram-positive and the thin, single-layered murein of gram-negative bacteria seems to follow an inside-to-outside growth strategy. New material is hooked in a relaxed state underneath the stress-bearing sacculus before it becomes inserted upon cleavage of covalent bonds in the layer(s) under tension. A model is presented that postulates that maintenance of bacterial shape is achieved by the enzyme complex copying the preexisting murein sacculus that plays the role of a template.
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              Control of cell shape in bacteria: helical, actin-like filaments in Bacillus subtilis.

              In the absence of an overt cytoskeleton, the external cell wall of bacteria has traditionally been assumed to be the primary determinant of cell shape. In the Gram-positive bacterium Bacillus subtilis, two related genes, mreB and mbl, were shown to be required for different aspects of cell morphogenesis. Subcellular localization of the MreB and Mbl proteins revealed that each forms a distinct kind of filamentous helical structure lying close to the cell surface. The distribution of the proteins in different species of bacteria, and the similarity of their sequence to eukaryotic actins, suggest that the MreB-like proteins have a cytoskeletal, actin-like role in bacterial cell morphogenesis.

                Author and article information

                Role: Reviewing Editor
                eLife Sciences Publications, Ltd
                22 February 2018
                : 7
                [1 ]deptDepartment of Molecular and Cellular Biology Harvard University CambridgeUnited States
                [2 ]MRC Laboratory of Molecular Biology CambridgeUnited Kingdom
                [3 ]Harvard John A. Paulson School of Engineering and Applied Sciences CambridgeUnited States
                [4 ]deptDepartment of Microbiology and Immunology Harvard University CambridgeUnited States
                [5 ]Leibniz Institute of Polymer Research DresdenGermany
                [6 ]deptDepartment of Chemistry and Chemical Biology Harvard University CambridgeUnited States
                Aix Marseille University-CNRS UMR7283 France
                Aix Marseille University-CNRS UMR7283 France
                Author notes

                These authors contributed equally to this work.

                © 2018, Hussain et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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                Funded by: FundRef http://dx.doi.org/10.13039/100000001, National Science Foundation;
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                Funded by: FundRef http://dx.doi.org/10.13039/501100000265, Medical Research Council;
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                Funded by: FundRef http://dx.doi.org/10.13039/100000011, Howard Hughes Medical Institute;
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                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
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                Funded by: Searle Scholar Fellowship;
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                Funded by: FundRef http://dx.doi.org/10.13039/100000879, Alfred P. Sloan Foundation;
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                Funded by: Smith Family Award;
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                Funded by: FundRef http://dx.doi.org/10.13039/501100001663, Volkswagen Foundation;
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                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Research Article
                Microbiology and Infectious Disease
                Custom metadata
                MreB filaments bind, orient, and move along the direction of greatest membrane curvature, thus orienting the insertion of new glycan strands around the cell circumference in a manner that may help establish and maintain rod shape.

                Life sciences

                cell shape, self organization, cell wall, bacillus subtilis, peptidoglycan, actin, b. subtilis, e. coli


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