Rotate into shape: MreB and bacterial morphogenesis.

MreB, the bacterial actin homologue, plays a vital role in determining cell shape, but the mechanisms by which it actually functions have remained largely mysterious. Recent studies now shed new light on MreB, demonstrating that it associates with many cell-wall synthesis enzymes, including a newly identified family of proteins that mediate teichoic acid synthesis in Gram-positive bacteria. Furthermore, MreB filaments dynamically rotate around the cell circumference in a manner dependent on the cell-wall assembly machinery. Thus, MreB may function to spatially organize the enzymatic activities required for proper bacterial growth (see Figure 1). In nearly all bacteria, cell shape is determined by the structure of the cell wall, a rigid crosslinked meshwork that counteracts the cellular turgor pressure. Bacteria can be generally separated into Gram-negative species that have a thin peptidoglycan (PG) cell wall and both an inner and outer membrane, and Gram-positive species with only one membrane and a thick cell wall composed of both PG and wall teichoic acids (WTAs). In both groups, PG biosynthesis is carried out by a series of Mur enzymes that synthesize PG precursors in the cytoplasm and several penicillin binding proteins (PBPs) that polymerize and crosslink these subunits once they are exported (Vollmer and Seligman, 2010). Given that both MreB and the various PG and WTA enzymes are required for proper growth, the challenge has been to develop a biophysical understanding of the interaction between these two systems. An important step forward was recently made in three independent papers that link the dynamics of MreB to cell-wall synthesis in two evolutionary distinct organisms, the Gram-negative bacterium Escherichia coli (van Teeffelen et al, 2011) and the Gram-positive Bacillus subtilis (Dominguez-Escobar et al, 2011; Garner et al, 2011). All three studies found that MreB polymers rotate around the long axis of the bacterial cell on a time scale of 1–5 min. While MreB motion had previously been attributed to its polymerization, these new studies show that this rotation is not caused by polymerization but rather depends on cell-wall synthesis activity. Specifically, if cell-wall precursors are depleted or cell-wall synthesis enzymes inhibited with antibiotic drugs, then MreB rotation stops. In B. subtilis, such rotational motion was observed for the PG transpeptidases PbpH and Pbp2A as well as for the MreB-associated proteins MreC, MreD, and RodA, which are believed to be part of cellwall synthesis complexes. In the E. coli system, analysis of MreB dynamics supported a quantitative model in which processive cell-wall assembly enzymes are physically linked to MreB such that PG synthesis pulls MreB around the cell