The normal, unmodified glycan strands of bacterial peptidoglycan consist of alternating residues of β-1,4-linked N-acetylmuramic acid and N-acetylglucosamine. In many species the glycan strands ...become modified after their insertion into the cell wall. This review describes the structure of secondary modifications and of attachment sites of surface polymers in the glycan strands of peptidoglycan. It also provides an overview of the occurrence of these modifications in various bacterial species. Recently, enzymes responsible for the N-deacetylation, N-glycolylation and O-acetylation of the glycan strands were identified. The presence of these modifications affects the hydrolysis of peptidoglycan and its enlargement during cell growth. Glycan strands are frequently deacetylated and/or O-acetylated in pathogenic species. These alterations affect the recognition of bacteria by host factors, and contribute to the resistance of bacteria to host defence factors such as lysozyme.
Summary
Most bacteria surround their cytoplasmic membrane with a net‐like, elastic heteropolymer, the peptidoglycan sacculus, to protect themselves from bursting due to the turgor and to maintain ...cell shape. It has been assumed that growing bacteria require peptidoglycan hydrolases to open meshes in the peptidoglycan net allowing the insertion of the newly synthesized material for surface expansion. However, peptidoglycan hydrolases essential for bacterial growth have long remained elusive. In this issue of Molecular Microbiology Singh et al. () report the identification in Escherichia coli of three new DD‐endopeptidases (Spr, YdhO and YebA) which are collectively required for peptidoglycan growth. Cells depleted of the three enzymes fail to incorporate new peptidoglycan, indicating that the cleavage of cross‐links by the new endopeptidases is needed for surface growth of the sacculus. These results are corroborated by recent data showing that Bacillus subtilis cells require the DL‐endopeptidase activity of CwlO or LytE for growth.
Bacteria surround their cell membrane with a net-like peptidoglycan layer, called sacculus, to protect the cell from bursting and maintain its cell shape. Sacculus growth during elongation and cell ...division is mediated by dynamic and transient multiprotein complexes, the elongasome and divisome, respectively. In this Review we present our current understanding of how peptidoglycan synthases are regulated by multiple and specific interactions with cell morphogenesis proteins that are linked to a dynamic cytoskeletal protein, either the actin-like MreB or the tubulin-like FtsZ. Several peptidoglycan synthases and hydrolases require activation by outer-membrane-anchored lipoproteins. We also discuss how bacteria achieve robust cell wall growth under different conditions and stresses by maintaining multiple peptidoglycan enzymes and regulators as well as different peptidoglycan growth mechanisms, and we present the emerging role of LD-transpeptidases in peptidoglycan remodelling.
In the recent decade, our view on the organization of the bacterial cell has been revolutionized by the identification of cytoskeletal elements. Most bacterial species have structural homologs of ...actin and tubulin that assemble into dynamic, filamentous structures at precisely defined sub-cellular locations. The essential cell division protein FtsZ forms a dynamic ring at mid-cell and is similar in its structure to tubulin. Proteins of the MreB family, which are structural homologs of actin, assemble into helical or straight filaments in the bacterial cytoplasm. As in eukaryotic cells, the bacterial cytoskeleton drives essential cellular processes such as cell division, cell wall growth, DNA movement, protein targeting, and alignment of organelles. Different high-throughput assays have been developed to search for inhibitors of components of the bacterial cytoskeleton. Cell-based assays for the detection of cell division inhibitors as well as FtsZ GTPase assays led to the identification of several compounds that inhibit the polymerization of FtsZ, by this blocking bacterial cell division. Such inhibitors might not only be valuable tools for basic research, but might also lead to novel therapeutic agents against pathogenic bacteria. For example, the polyphenol dichamanetin, the 2-alkoxycarbonylaminopyridine SRI-3072, and the benzophenanthridine alkaloid sanguinarine inhibit the GTPase activity of FtsZ and exhibit antimicrobial activity.
The periplasmic murein (peptidoglycan) sacculus is a giant macromolecule made of glycan strands cross-linked by short peptides completely surrounding the cytoplasmic membrane to protect the cell from ...lysis due to its internal osmotic pressure. More than 50 different muropeptides are released from the sacculus by treatment with a muramidase.
Escherichia coli has six murein synthases which enlarge the sacculus by transglycosylation and transpeptidation of lipid II precursor. A set of twelve periplasmic murein hydrolases (autolysins) release murein fragments during cell growth and division. Recent data on the in vitro murein synthesis activities of the murein synthases and on the interactions between murein synthases, hydrolases and cell cycle related proteins are being summarized. There are different models for the architecture of murein and for the incorporation of new precursor into the sacculus. We present a model in which morphogenesis of the rod-shaped
E. coli is driven by cytoskeleton elements competing for the control over the murein synthesis multi-enzyme complexes.
How bacteria grow and divide while retaining a defined shape is a fundamental question in microbiology, but technological advances are now driving a new understanding of how the shape-maintaining ...bacterial peptidoglycan sacculus grows. In this Review, we highlight the relationship between peptidoglycan synthesis complexes and cytoskeletal elements, as well as recent evidence that peptidoglycan growth is regulated from outside the sacculus in Gram-negative bacteria. We also discuss how growth of the sacculus is sensitive to mechanical force and nutritional status, and describe the roles of peptidoglycan hydrolases in generating cell shape and of D-amino acids in sacculus remodelling.
Peptidoglycan forms a net-like sacculus made of glycan strands crosslinked by peptides. The length of the glycan strands and the degree of crosslinkage vary with bacterial species, strains and growth ...conditions. Several models for the three-dimensional architecture of peptidoglycan have been proposed, some of which have been tested experimentally. The new data support a layered model in Gram-negative bacteria, and a more elaborate peptidoglycan architecture, with bands made of coiled bundles of glycan strands, in the rod-shaped Bacillus subtilis . However, many questions remain unanswered and, therefore, more data and more models are required to decipher the complex cell wall architecture in bacteria.
Summary
Streptococcus pneumoniae is an oval‐shaped Gram‐positive 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.
The physiology of bacterial cell division Egan, Alexander J. F.; Vollmer, Waldemar
Annals of the New York Academy of Sciences,
January 2013, Volume:
1277, Issue:
1
Journal Article
Peer reviewed
Open access
Bacterial cell division is facilitated by the divisome, a dynamic multiprotein assembly localizing at mid‐cell to synthesize the stress‐bearing peptidoglycan and to constrict all cell envelope ...layers. Divisome assembly occurs in two steps and involves multiple interactions between more than 20 essential and accessory cell division proteins. Well before constriction and while the cell is still elongating, the tubulin‐like FtsZ and early cell division proteins form a ring‐like structure at mid‐cell. Cell division starts once certain peptidoglycan enzymes and their activators have moved to the FtsZ‐ring. Gram‐negative bacteria like Escherichia coli simultaneously synthesize and cleave the septum peptidoglycan during division leading to a constriction. The outer membrane constricts together with the peptidoglycan layer with the help of the transenvelope spanning Tol–Pal system.
Although the peptidoglycan cell wall is an essential structural and morphological feature of most bacterial cells, the extracytoplasmic enzymes involved in its synthesis are frequently dispensable ...under standard culture conditions. By modulating a single growth parameter-extracellular pH-we discovered a subset of these so-called 'redundant' enzymes in
are required for maximal fitness across pH environments. Among these pH specialists are the class A penicillin binding proteins PBP1a and PBP1b; defects in these enzymes attenuate growth in alkaline and acidic conditions, respectively. Genetic, biochemical, and cytological studies demonstrate that synthase activity is required for cell wall integrity across a wide pH range and influences pH-dependent changes in resistance to cell wall active antibiotics. Altogether, our findings reveal previously thought to be redundant enzymes are instead specialized for distinct environmental niches. This specialization may ensure robust growth and cell wall integrity in a wide range of conditions.
This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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