From models to pathogens: how much have we learned aboutStreptococcus pneumoniaecell division?

Abstract

SummaryStreptococcus pneumoniae is an oval-shaped Grampositive coccus that lives in intimate association with its human host, both as a commensal and pathogen. The seriousness of pneumococcal infections and the spread of multi-drug resistant strains call for new lines of intervention. Bacterial cell division is an attractive target to develop antimicrobial drugs. This review discusses the recent advances in understanding S. pneumoniae growth and division, in comparison with the best studied rod-shaped models, Escherichia coli and Bacillus subtilis. To maintain their shape, these bacteria propagate by peripheral and septal peptidoglycan synthesis, involving proteins that assemble into distinct complexes called the elongasome and the divisome, respectively. Many of these proteins are conserved in S. pneumoniae, supporting the notion that the ovococcal shape is also achieved by rounds of elongation and division. Importantly, S. pneumoniae and close relatives with similar morphology differ in several aspects from the model rods. Overall, the data support a model in which a single large machinery, containing both the peripheral and septal peptidoglycan synthesis complexes, assembles at midcell and governs growth and division. The mechanisms generating the ovococcal or coccal shape in lactic-acid bacteria have likely evolved by gene reduction from a rod-shaped ancestor of the same group.

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

“…Markerless deletions of the division genes, mapZ (alternative name, locZ) and divIVA, fused short (20-amino acid) stretches from the beginning and end of the genes to maintain possible translational coupling (see Tables S1 and S2). The phenotypes of the markerless ⌬mapZ and ⌬divIVA mutants were similar to those reported previously for other mapZ and divIVA mutants (41)(42)(43).…”

“…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.…”

Lyme disease and relapsing feverBorreliaelongate through zones of peptidoglycan synthesis that mark division sites of daughter cells

“…Perhaps more importantly, the spatial and temporal regulation of PG synthesis contributing to either cell elongation or septum formation are vastly different between B. burgdorferi and S. pneumoniae, ultimately shaping their cell morphology. In S. pneumoniae, cell elongation occurs at the same time and place as septum formation, such that cells adopt a prolate spheroid shape (6,(25)(26)(27)(28)(29). This is in contrast to B. burgdorferi, in which cell elongation and septum formation are largely uncoupled, resulting in long, rod-shaped cells.…”

SpyAD, a Moonlighting Protein of Group A Streptococcus Contributing to Bacterial Division and Host Cell Adhesion

“…Recent investigations have clearly indicated that the divisome of E. coli (50), S. pneumoniae (51), and S. aureus (49) are built by a complex network of interactions where each component interacts with multiple partners. By homology search, we identified the GAS counterpart of most genes involved in division of S. pneumoniae (see Table S4 in the supplemental material) and we predict that, in addition to FtsZ, SpyAD possibly interacts with other components of the GAS cell division apparatus and/or the peptidoglycan synthesis machinery located in the septum of Gram-positive cocci (52,53). Indeed, SpyAD shares structural features of many divisome interacting proteins including coiled-coil arrangements and a leucine zipper motif.…”