The Requirement for Pneumococcal MreC and MreD Is Relieved by Inactivation of the Gene Encoding PBP1a

Abstract

Three basic patterns of peptidoglycan (PG) synthesis have emerged from the study of rod-shaped (bacillus), spherical (coccus), and ellipsoid (ovococcus) bacteria (reviewed in references 12, 71, and 72). In rod-shaped bacteria, like Escherichia coli, Bacillus subtilis, and Caulobacter crescentus, PG synthesis occurs at two locations catalyzed by distinct sets of proteins (12,35,36,71). Lateral PG synthesis elongates the side walls of these bacteria and results in their rod shape (12,35,71). Lateral PG synthesis is mediated by actin-like MreB paralogue proteins, which form filamentous helical structures in spirals over the length of cells (12,35,66). MreB is thought to organize the MreC and MreD proteins, which in turn recruit specific penicillin-binding proteins (PBPs) and other division proteins that catalyze lateral PG formation (26,54,55,70). Septal PG synthesis is organized by FtsZ ring formation, followed by the orderly assembly of the divisome complex, which includes a set of PBPs different from those involved in lateral PG synthesis (16,22,23). The mutational interruption of lateral or septal PG synthesis of rod-shaped bacteria generally results in the formation of spherical or elongated cells, respectively (3, 4, 9, 31). Although useful, this two-state model is obviously an oversimplification (35), and recent results reveal that MreB, MreC, MreD, and specific PBPs also form annular rings adjacent to FtsZ rings at the septa of dividing E. coli cells (67). Moreover, some PBPs and division regulators, such as PBP1 and GpsB of B. subtilis, shuttle between the lateral and septal PG synthesis machineries (9).Much less is known about the mechanisms of PG synthesis in coccus and ovococcus species. In spherical species, such as Staphylococcus aureus, only a septal PG synthesis machinery seems to be present (20,47,72), although S. aureus still encodes homologues of proteins like MreC and MreD that mediate lateral PG synthesis in rod-shaped bacteria (35). In contrast, ovococcus species, such as Streptococcus pneumoniae and Lactococcus lactis, form American football-shaped cells by a combination of peripheral sidewall and septal PG synthesis that occurs in the midcell regions of dividing cells (Fig. 1) (11,42). Ovococcus species lack an MreB homologue, and peripheral and septal PG synthesis are likely coordinated with and organized by FtsZ ring formation (64,65,72). Because two modes of PG biosynthesis are required to form ellipsoidshaped bacteria, models have been proposed for two different PG synthesis machineries (18,21,33,72). Based on the composition of the complexes in rod-shaped cells, it has been hypothesized that specific sets of homologous cell division proteins mediate peripheral (MreC, MreD, RodA, and PBP2b) and septal (FtsZ, EzrA, PBP2x, FtsW, and DivIB/FtsL/DivIC) PG synthesis in ovococcus bacteria (72). A recent study correlating the effects of mutations or antibiotic treatments to changes in cell shapes supports the idea that the PBP2x and PBP2b class B transpeptidases are associated with septal and p...

Minimal Peptidoglycan (PG) Turnover in Wild-Type and PG Hydrolase and Cell Division Mutants of Streptococcus pneumoniae D39 Growing Planktonically and in Host-Relevant Biofilms

“…⌬pbp1a mutants have the distinctive phenotype of forming considerably smaller but normally shaped cells compared to their pbp1a ϩ parent strain (Fig. 8, top row) (76). The persistence of stable PG hemispheres was not altered by the ⌬pbp1a mutation or the decrease in cell size and volume.…”

“…8, top row). Finally, we examined the PG stability in a ⌬pbp1a mutant lacking the major class A PBP1a, which likely functions in both septal and peripheral (i.e., midcell sidewall) PG synthesis (43,76). ⌬pbp1a mutants have the distinctive phenotype of forming considerably smaller but normally shaped cells compared to their pbp1a ϩ parent strain (Fig.…”

Supramolecular structure in the membrane of Staphylococcus aureus

“…S12 and S13), reminiscent of the PlsY-depleted phenotype. The lack of an apparent phenotype for the single mreC mutation was interesting given its importance in other organisms (34). Genome sequencing of two individual mreC mutants revealed one single nucleotide polymorphism in each strain leading to an amino acid substitution (SI Appendix, Whole Genome Sequencing).…”

Control of cell division in Streptococcus pneumoniae by the conserved Ser/Thr protein kinase StkP

“…Consistent with this notion, FtsZ has been found to interact directly with PBP2b (i.e., the S. pneumoniae PBP most likely involved in lateral cell-wall elongation) in E. coli two-hybrid assays (57,58). Interestingly, S. pneumoniae MreC/D recently were shown to direct peripheral PG synthesis (59). Also, Lactococcus lactis, a phylogenetically close relative of S. pneumoniae, has been shown recently to undergo a coccus-to-rod transition as a result of unbalanced activity of the cell-synthesis machineries (60).…”