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Nature Reviews. Microbiology Aug 2020Bacteria surround their cell membrane with a net-like peptidoglycan layer, called sacculus, to protect the cell from bursting and maintain its cell shape. Sacculus... (Review)
Review
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.
Topics: Bacteria; Bacterial Proteins; Cell Membrane; Cell Wall; Cytoskeletal Proteins; Peptidoglycan
PubMed: 32424210
DOI: 10.1038/s41579-020-0366-3 -
EcoSal Plus Jan 2021Peptidoglycan is a defining feature of the bacterial cell wall. Initially identified as a target of the revolutionary beta-lactam antibiotics, peptidoglycan has become a...
Peptidoglycan is a defining feature of the bacterial cell wall. Initially identified as a target of the revolutionary beta-lactam antibiotics, peptidoglycan has become a subject of much interest for its biology, its potential for the discovery of novel antibiotic targets, and its role in infection. Peptidoglycan is a large polymer that forms a mesh-like scaffold around the bacterial cytoplasmic membrane. Peptidoglycan synthesis is vital at several stages of the bacterial cell cycle: for expansion of the scaffold during cell elongation and for formation of a septum during cell division. It is a complex multifactorial process that includes formation of monomeric precursors in the cytoplasm, their transport to the periplasm, and polymerization to form a functional peptidoglycan sacculus. These processes require spatio-temporal regulation for successful assembly of a robust sacculus to protect the cell from turgor and determine cell shape. A century of research has uncovered the fundamentals of peptidoglycan biology, and recent studies employing advanced technologies have shed new light on the molecular interactions that govern peptidoglycan synthesis. Here, we describe the peptidoglycan structure, synthesis, and regulation in rod-shaped bacteria, particularly , with a few examples from and other diverse organisms. We focus on the pathway of peptidoglycan sacculus elongation, with special emphasis on discoveries of the past decade that have shaped our understanding of peptidoglycan biology.
Topics: Cell Division; Cell Membrane; Cell Wall; Escherichia coli; Peptidoglycan
PubMed: 33470191
DOI: 10.1128/ecosalplus.ESP-0010-2020 -
Microbiology Spectrum May 2019has a complex cell wall that plays key roles in cell shape maintenance, growth and cell division, and interactions with components of the human host. The peptidoglycan... (Review)
Review
has a complex cell wall that plays key roles in cell shape maintenance, growth and cell division, and interactions with components of the human host. The peptidoglycan has a heterogeneous composition with more than 50 subunits (muropeptides)-products of several peptidoglycan-modifying enzymes. The amidation of glutamate residues in the stem peptide is needed for efficient peptide cross-linking, and peptides with a dipeptide branch prevail in some beta-lactam-resistant strains. The glycan strands are modified by deacetylation of -acetylglucosamine residues and -acetylation of -acetylmuramic acid residues, and both modifications contribute to pneumococcal resistance to lysozyme. The glycan strands carry covalently attached wall teichoic acid and capsular polysaccharide. Pneumococci are unique in that the wall teichoic acid and lipoteichoic acid contain the same unusually complex repeating units decorated with phosphoryl choline residues, which anchor the choline-binding proteins. The structures of lipoteichoic acid and the attachment site of wall teichoic acid to peptidoglycan have recently been revised. During growth, pneumococci assemble their cell walls at midcell in coordinated rounds of cell elongation and division, leading to the typical ovococcal cell shape. Cell wall growth depends on the cytoskeletal FtsA and FtsZ proteins and is regulated by several morphogenesis proteins that also show patterns of dynamic localization at midcell. Some of the key regulators are phosphorylated by StkP and dephosphorylated by PhpP to facilitate robust selection of the division site and plane and to maintain cell shape.
Topics: Acetylation; Acetylglucosamine; Bacterial Proteins; Cell Cycle; Cell Division; Cell Wall; Choline; Cytoskeletal Proteins; Humans; Lipopolysaccharides; Muramic Acids; Muramidase; Operon; Penicillin Resistance; Peptidoglycan; Phosphorylation; Polysaccharides; Streptococcus pneumoniae; Teichoic Acids; beta-Lactam Resistance
PubMed: 31172911
DOI: 10.1128/microbiolspec.GPP3-0018-2018 -
Viruses Apr 2021Antibiotic-resistant pathogens are increasingly more prevalent and problematic. Traditional antibiotics are no longer a viable option for dealing with these... (Review)
Review
Antibiotic-resistant pathogens are increasingly more prevalent and problematic. Traditional antibiotics are no longer a viable option for dealing with these multidrug-resistant microbes and so new approaches are needed. Bacteriophage-derived proteins such as endolysins could offer one effective solution. Endolysins are bacteriophage-encoded peptidoglycan hydrolases that act to lyse bacterial cells by targeting their cell's wall, particularly in Gram-positive bacteria due to their naturally exposed peptidoglycan layer. These lytic enzymes have received much interest from the scientific community in recent years for their specificity, mode of action, potential for engineering, and lack of resistance mechanisms. Over the past decade, a renewed interest in endolysin therapy has led to a number of successful applications. Recombinant endolysins have been shown to be effective against prominent pathogens such as MRSA, strains in biofilm formation, and . Endolysins have also been studied in combination with other antimicrobials, giving a synergistic effect. Although endolysin therapy comes with some regulatory and logistical hurdles, the future looks promising, with the emergence of engineered "next-generation" lysins. This review will focus on the likelihood that endolysins will become a viable new antimicrobial therapy and the challenges that may have to be overcome along the way.
Topics: Animals; Bacteriophages; Cell Wall; Endopeptidases; Gram-Positive Bacterial Infections; Humans; Peptidoglycan; Phage Therapy
PubMed: 33920965
DOI: 10.3390/v13040680 -
Sub-cellular Biochemistry 2019The peptidoglycan sacculus is a net-like polymer that surrounds the cytoplasmic membrane in most bacteria. It is essential to maintain the bacterial cell shape and... (Review)
Review
The peptidoglycan sacculus is a net-like polymer that surrounds the cytoplasmic membrane in most bacteria. It is essential to maintain the bacterial cell shape and protect from turgor. The peptidoglycan has a basic composition, common to all bacteria, with species-specific variations that can modify its biophysical properties or the pathogenicity of the bacteria. The synthesis of peptidoglycan starts in the cytoplasm and the precursor lipid II is flipped across the cytoplasmic membrane. The new peptidoglycan strands are synthesised and incorporated into the pre-existing sacculus by the coordinated activities of peptidoglycan synthases and hydrolases. In the model organism Escherichia coli there are two complexes required for the elongation and division. Each of them is regulated by different proteins from both the cytoplasmic and periplasmic sides that ensure the well-coordinated synthesis of new peptidoglycan.
Topics: Cell Wall; Escherichia coli; Peptidoglycan
PubMed: 31214986
DOI: 10.1007/978-3-030-18768-2_5 -
Annual Review of Microbiology Oct 2021Most bacteria are surrounded by a peptidoglycan cell wall that defines their shape and protects them from osmotic lysis. The expansion and division of this structure... (Review)
Review
Most bacteria are surrounded by a peptidoglycan cell wall that defines their shape and protects them from osmotic lysis. The expansion and division of this structure therefore plays an integral role in bacterial growth and division. Additionally, the biogenesis of the peptidoglycan layer is the target of many of our most effective antibiotics. Thus, a better understanding of how the cell wall is built will enable the development of new therapies to combat the rise of drug-resistant bacterial infections. This review covers recent advances in defining the mechanisms involved in assembling the peptidoglycan layer with an emphasis on discoveries related to the function and regulation of the cell elongation and division machineries in the model organisms and .
Topics: Bacillus subtilis; Bacterial Proteins; Cell Wall; Cytoskeletal Proteins; Peptidoglycan
PubMed: 34351794
DOI: 10.1146/annurev-micro-020518-120056 -
Microbiology Spectrum Dec 2015Bacterial endospores possess multiple integument layers, one of which is the cortex peptidoglycan wall. The cortex is essential for the maintenance of spore core... (Review)
Review
Bacterial endospores possess multiple integument layers, one of which is the cortex peptidoglycan wall. The cortex is essential for the maintenance of spore core dehydration and dormancy and contains structural modifications that differentiate it from vegetative cell peptidoglycan and determine its fate during spore germination. Following the engulfment stage of sporulation, the cortex is synthesized within the intermembrane space surrounding the forespore. Proteins responsible for cortex synthesis are produced in both the forespore and mother cell compartments. While some of these proteins also contribute to vegetative cell wall synthesis, others are sporulation specific. In order for the bacterial endospore to germinate and resume metabolism, the cortex peptidoglycan must first be degraded through the action of germination-specific lytic enzymes. These enzymes are present, yet inactive, in the dormant spore and recognize the muramic-δ-lactam modification present in the cortex. Germination-specific lytic enzymes across Bacillaceae and Clostridiaceae share this specificity determinant, which ensures that the spore cortex is hydrolyzed while the vegetative cell wall remains unharmed. Bacillus species tend to possess two redundant enzymes, SleB and CwlJ, capable of sufficient cortex degradation, while the clostridia have only one, SleC. Additional enzymes are often present that cannot initiate the cortex degradation process, but which can increase the rate of release of small fragments into the medium. Between the two families, the enzymes also differ in the enzymatic activities they possess and the mechanisms acting to restrict their activation until germination has been initiated.
Topics: Bacteria; Bacterial Proteins; Cell Wall; Peptidoglycan; Spores, Bacterial
PubMed: 27337277
DOI: 10.1128/microbiolspec.TBS-0005-2012 -
Biochemistry Jul 2017Cellular mechanical properties play an integral role in bacterial survival and adaptation. Historically, the bacterial cell wall and, in particular, the layer of... (Review)
Review
Cellular mechanical properties play an integral role in bacterial survival and adaptation. Historically, the bacterial cell wall and, in particular, the layer of polymeric material called the peptidoglycan were the elements to which cell mechanics could be primarily attributed. Disrupting the biochemical machinery that assembles the peptidoglycan (e.g., using the β-lactam family of antibiotics) alters the structure of this material, leads to mechanical defects, and results in cell lysis. Decades after the discovery of peptidoglycan-synthesizing enzymes, the mechanisms that underlie their positioning and regulation are still not entirely understood. In addition, recent evidence suggests a diverse group of other biochemical elements influence bacterial cell mechanics, may be regulated by new cellular mechanisms, and may be triggered in different environmental contexts to enable cell adaptation and survival. This review summarizes the contributions that different biomolecular components of the cell wall (e.g., lipopolysaccharides, wall and lipoteichoic acids, lipid bilayers, peptidoglycan, and proteins) make to Gram-negative and Gram-positive bacterial cell mechanics. We discuss the contribution of individual proteins and macromolecular complexes in cell mechanics and the tools that make it possible to quantitatively decipher the biochemical machinery that contributes to bacterial cell mechanics. Advances in this area may provide insight into new biology and influence the development of antibacterial chemotherapies.
Topics: Adaptation, Physiological; Cell Membrane; Cell Wall; Gram-Negative Bacteria; Gram-Positive Bacteria; Lipid Bilayers; Lipopolysaccharides; Microbial Viability; Peptidoglycan; Teichoic Acids
PubMed: 28666084
DOI: 10.1021/acs.biochem.7b00346 -
FEMS Microbiology Reviews Nov 2018Planctomycetes are ubiquitous, environmentally and biotechnologically important bacteria that are key players in global carbon and nitrogen cycles. Ever since their... (Review)
Review
Planctomycetes are ubiquitous, environmentally and biotechnologically important bacteria that are key players in global carbon and nitrogen cycles. Ever since their first discovery in the 1920s they seemed to blur the prokaryote /eukaryote dichotomy. After initially being described as fungi and reclassified as bacteria later, they were still thought to feature a nucleus-like compartment surrounding their highly condensed DNA. Also, an endocytosis-like uptake mechanism for macromolecules was described. Besides these eukaryotic hallmark traits, Planctomycetes seemed to lack typical bacterial features such as a peptidoglycan cell wall or the universal bacterial cell division protein FtsZ, while mostly dividing by polar budding instead of binary fission. Thus, Planctomycetes were speculated to be ancestral to both, bacteria and eukaryotes. With the advent of novel microscopic techniques, along with the development of genetic tools for Planctomycetes, some of these hypotheses were revisited. Surprisingly, Planctomycetes were found to possess a peptidoglycan cell wall and to comprise a cell plan comparable to other Gram-negative bacteria as the nucleus-like structure is rather an invagination of the cytoplasmic membrane than a cohesive compartment. These finding challenge the idea of a eukaryotic ancestry of the phylum, as Planctomycetes now appear similar, yet distinct to other bacteria.
Topics: Biological Evolution; Cell Wall; Gram-Negative Bacteria; Peptidoglycan; Planctomycetales; Species Specificity
PubMed: 30052954
DOI: 10.1093/femsre/fuy029 -
Nature Mar 2023Gram-negative bacteria surround their cytoplasmic membrane with a peptidoglycan (PG) cell wall and an outer membrane (OM) with an outer leaflet composed of...
Gram-negative bacteria surround their cytoplasmic membrane with a peptidoglycan (PG) cell wall and an outer membrane (OM) with an outer leaflet composed of lipopolysaccharide (LPS). This complex envelope presents a formidable barrier to drug entry and is a major determinant of the intrinsic antibiotic resistance of these organisms. The biogenesis pathways that build the surface are also targets of many of our most effective antibacterial therapies. Understanding the molecular mechanisms underlying the assembly of the Gram-negative envelope therefore promises to aid the development of new treatments effective against the growing problem of drug-resistant infections. Although the individual pathways for PG and OM synthesis and assembly are well characterized, almost nothing is known about how the biogenesis of these essential surface layers is coordinated. Here we report the discovery of a regulatory interaction between the committed enzymes for the PG and LPS synthesis pathways in the Gram-negative pathogen Pseudomonas aeruginosa. We show that the PG synthesis enzyme MurA interacts directly and specifically with the LPS synthesis enzyme LpxC. Moreover, MurA was shown to stimulate LpxC activity in cells and in a purified system. Our results support a model in which the assembly of the PG and OM layers in many proteobacterial species is coordinated by linking the activities of the committed enzymes in their respective synthesis pathways.
Topics: Cell Wall; Lipopolysaccharides; Bacterial Outer Membrane; Pseudomonas aeruginosa; Peptidoglycan
PubMed: 36859542
DOI: 10.1038/s41586-023-05750-0