Mreb

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MreB is a protein found in bacteria that has been identified as a homologue of actin, as indicated by similarities in tertiary structure and conservation of active site peptide sequence. The conservation of protein structure suggests the common ancestry of the cytoskeletal elements formed by actin and MreB, found in prokaryotes. Indeed, recent studies have found that MreB proteins polymerize to form filaments that are similar to actin microfilaments. MreB controls the width of rod-shaped bacteria, such as Escherichia coli. A mutant E. Also, bacteria that are naturally spherical do not have the gene encoding MreB.

Mreb

Although many prospective antibiotic targets are known, bacterial infections and resistance to antibiotics remain a threat to public health partly because the druggable potentials of most of these targets have yet to be fully tapped for the development of a new generation of therapeutics. The prokaryotic actin homolog MreB is one of the important antibiotic targets that are yet to be significantly exploited. MreB is a bacterial cytoskeleton protein that has been widely studied and is associated with the determination of rod shape as well as important subcellular processes including cell division, chromosome segregation, cell wall morphogenesis, and cell polarity. Notwithstanding that MreB is vital and conserved in most rod-shaped bacteria, no approved antibiotics targeting it are presently available. Here, the status of targeting MreB for the development of antibiotics is concisely summarized. Expressly, the known therapeutic targets and inhibitors of MreB are presented, and the way forward in the search for a new generation of potent inhibitors of MreB briefly discussed. The emergence of antibiotic-resistant bacterial strains White et al. Nonetheless, the full druggable potentials of most bacterial pharmacological targets have yet to be tapped, and it is not surprising that few antibiotics have been released into the drug market in the past several years Conly and Johnston, The bacterial actin-like MreB is a potential therapeutic target Kruse et al. As an ATPase whose primary function involves coordinating bacterial cell wall biosynthesis Figge et al. MreB is a promising drug target because it is conserved and essential in most rod-shaped bacteria Varley and Stewart, ; Costa and Anton, , ; Burger et al. Notwithstanding that much is known about the structure and function of MreB and the possibility of targeting it with inhibitors Kruse et al. In this mini-review, the status of targeting MreB for the development of antibiotics is concisely summarized. MreB is referred to as the prokaryotic actin by virtue of the similarity between its monomeric three-dimensional tertiary structure and that of eukaryotic actin Van Den Ent et al.

Unlike the membrane-bound periplasmic truncations RodZ 1— and RodZ 1—mreb, a small truncation in the RodZ cytoplasmic domain RodZ 59— shows a clear change in MreB curvature preference with both a decreased enrichment near zero and less of a depletion from mreb with positive Gaussian curvature Fig.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. The actin-like protein MreB has been proposed to coordinate the synthesis of the cell wall to determine cell shape in bacteria.

MreB is a protein found in bacteria that has been identified as a homologue of actin, as indicated by similarities in tertiary structure and conservation of active site peptide sequence. The conservation of protein structure suggests the common ancestry of the cytoskeletal elements formed by actin and MreB, found in prokaryotes. Indeed, recent studies have found that MreB proteins polymerize to form filaments that are similar to actin microfilaments. MreB controls the width of rod-shaped bacteria, such as Escherichia coli. A mutant E. Also, bacteria that are naturally spherical do not have the gene encoding MreB. Prokaryotes carrying the mreB gene can also be helical in shape. MreB has long been thought to form a helical filament underneath the cytoplasmic membrane. However, this model has been brought into question by three recent publications showing that filaments cannot be seen by electron cryotomography and that GFP-MreB can be seen as patches moving around the cell circumference. It has also been shown to interact with several proteins that are proven to be involved in length growth for instance PBP2.

Mreb

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Work over the past decade has highlighted the pivotal role of the actin-like MreB family of proteins in the determination and maintenance of rod cell shape in bacteria. Early images of MreB localization revealed long helical filaments, which were suggestive of a direct role in governing cell wall architecture. However, several more recent, higher-resolution studies have questioned the existence or importance of the helical structures. In this Opinion article, I navigate a path through these conflicting reports, revive the helix model and summarize the key questions that remain to be answered. This is a preview of subscription content, access via your institution.

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Lewis, R. These fusions appeared patchy in raw images, but deconvolution algorithms biased toward finding ordered structures suggested extended helical structures. YodL and YisK possess shape-modifying activities that are suppressed by mutations in Bacillus subtilis mreB and mbl. Furchtgott, L. Growth of the stress-bearing and shape-maintaining murein sacculus of Escherichia coli. Gov't, P. This publication refers specifically to release 1. MreB: pilot or passenger of cell wall synthesis? These two reconstructions are similar to each other but represent the shape in a different framework. Nat Commun. Where are all the new antibiotics? Interference with the MreB activity renders cells mechanically less rigid 6 , and, in the absence of this, protein cells lose their rod-shaped morphology 7 , 8.

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Early studies in B. MreB and its homologs have been shown to interact and co-localize with cytoplasmic protein MurB-G , membrane-imbedded proteins MreD, MraY and RodA , as well as other molecules with large periplasmic domain in organism. It turned out that MreB filaments, and the associated cell wall synthetic machinery, move around the cell in a process that is driven by peptidoglycan synthesis 9 , 10 , Cold Spring Harb. Drug induced shape changes For mecillinam treatment, cells were grown overnight and subcultured in the morning into LB with sub-lethal concentrations of mecillinam 0. Recent advances in cryo-electron microscopy have demonstrated that T. For other comparisons see Supplementary Table 3. Garcia-Saez, A. Given the multitude of proteins that directly or indirectly interact with MreB to insert wall material Scheffers and Pinho, , not to mention the membrane and the cell wall itself, the properties of MreB filaments that determine curvature sensing could be subject to regulation. However, previous studies have not examined the MreB properties coupled to the ability to form an elongated cylindrical rod-like cell. The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography. Cell Systems.