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Advances in Applied Microbiology 2020The bacterial peptidoglycan layer forms a complex mesh-like structure that surrounds the cell, imparting rigidity to withstand cytoplasmic turgor and the ability to... (Review)
Review
The bacterial peptidoglycan layer forms a complex mesh-like structure that surrounds the cell, imparting rigidity to withstand cytoplasmic turgor and the ability to tolerate stress. As peptidoglycan has been the target of numerous clinically successful antimicrobials such as penicillin, the biosynthesis, remodeling and recycling of this polymer has been the subject of much interest. Herein, we review recent advances in the understanding of peptidoglycan biosynthesis and remodeling in a variety of different organisms. In order for bacterial cells to grow and divide, remodeling of cross-linked peptidoglycan is essential hence, we also summarize the activity of important peptidoglycan hydrolases and how their functions differ in various species. There is a growing body of evidence highlighting complex regulatory mechanisms for peptidoglycan metabolism including protein interactions, phosphorylation and protein degradation and we summarize key recent findings in this regard. Finally, we provide an overview of peptidoglycan recycling and how components of this pathway mediate resistance to drugs. In the face of growing antimicrobial resistance, these recent advances are expected to uncover new drug targets in peptidoglycan metabolism, which can be used to develop novel therapies.
Topics: Bacteria; Bacterial Proteins; Cytoskeleton; N-Acetylmuramoyl-L-alanine Amidase; Penicillin-Binding Proteins; Peptidoglycan; Phosphorylation; Protein Interaction Maps; Species Specificity; beta-Lactamases
PubMed: 32762868
DOI: 10.1016/bs.aambs.2020.04.001 -
Nature Jun 2022Linkages between the outer membrane of Gram-negative bacteria and the peptidoglycan layer are crucial for the maintenance of cellular integrity and enable survival in...
Linkages between the outer membrane of Gram-negative bacteria and the peptidoglycan layer are crucial for the maintenance of cellular integrity and enable survival in challenging environments. The function of the outer membrane is dependent on outer membrane proteins (OMPs), which are inserted into the membrane by the β-barrel assembly machine (BAM). Growing Escherichia coli cells segregate old OMPs towards the poles by a process known as binary partitioning, the basis of which is unknown. Here we demonstrate that peptidoglycan underpins the spatiotemporal organization of OMPs. Mature, tetrapeptide-rich peptidoglycan binds to BAM components and suppresses OMP foldase activity. Nascent peptidoglycan, which is enriched in pentapeptides and concentrated at septa, associates with BAM poorly and has little effect on its activity, leading to preferential insertion of OMPs at division sites. The synchronization of OMP biogenesis with cell wall growth results in the binary partitioning of OMPs as cells divide. Our study reveals that Gram-negative bacteria coordinate the assembly of two major cell envelope layers by rendering OMP biogenesis responsive to peptidoglycan maturation, a potential vulnerability that could be exploited in future antibiotic design.
Topics: Bacterial Outer Membrane Proteins; Cell Membrane; Cell Wall; Escherichia coli; Escherichia coli Proteins; Peptidoglycan; Protein Folding
PubMed: 35705811
DOI: 10.1038/s41586-022-04834-7 -
Molecular Immunology Feb 2019Insects lack an acquired immune system and rely solely on the innate immune system to combat microbial infection. The innate immunity of insects mainly depends on the... (Review)
Review
Insects lack an acquired immune system and rely solely on the innate immune system to combat microbial infection. The innate immunity of insects mainly depends on the interaction between the host's pattern recognition receptor (PRR) and pathogen-associated molecular pattern (PAMP). The peptidoglycan recognition proteins (PGRPs) family is the most important pattern recognition receptor (PRR) for insects. It can recognize the main component of the cell wall of the pathogenic microorganism, peptidoglycan (PGN), and plays an important role in the innate immunity of insects. In this paper, the structure, classification, and function of PGRPs is summarized, and the role of PGRPs in the innate immunity of insects is also discussed.
Topics: Animals; Immunity, Innate; Insect Proteins; Insecta; Peptidoglycan; Receptors, Pattern Recognition
PubMed: 30590209
DOI: 10.1016/j.molimm.2018.12.021 -
Biomolecules Apr 2023Bacteria must synthesize their cell wall and membrane during their cell cycle, with peptidoglycan being the primary component of the cell wall in most bacteria.... (Review)
Review
Bacteria must synthesize their cell wall and membrane during their cell cycle, with peptidoglycan being the primary component of the cell wall in most bacteria. Peptidoglycan is a three-dimensional polymer that enables bacteria to resist cytoplasmic osmotic pressure, maintain their cell shape and protect themselves from environmental threats. Numerous antibiotics that are currently used target enzymes involved in the synthesis of the cell wall, particularly peptidoglycan synthases. In this review, we highlight recent progress in our understanding of peptidoglycan synthesis, remodeling, repair, and regulation in two model bacteria: the Gram-negative and the Gram-positive . By summarizing the latest findings in this field, we hope to provide a comprehensive overview of peptidoglycan biology, which is critical for our understanding of bacterial adaptation and antibiotic resistance.
Topics: Peptidoglycan; Bacteria; Anti-Bacterial Agents; Cell Division; Cell Wall; Bacterial Proteins
PubMed: 37238589
DOI: 10.3390/biom13050720 -
Nature Communications Oct 2023Peptidoglycan, a gigadalton polymer, functions as the scaffold for bacterial cell walls and provides cell integrity. Peptidoglycan is remodelled by a large and diverse...
Peptidoglycan, a gigadalton polymer, functions as the scaffold for bacterial cell walls and provides cell integrity. Peptidoglycan is remodelled by a large and diverse group of peptidoglycan hydrolases, which control bacterial cell growth and division. Over the years, many studies have focused on these enzymes, but knowledge on their action within peptidoglycan mesh from a molecular basis is scarce. Here, we provide structural insights into the interaction between short peptidoglycan fragments and the entire sacculus with two evolutionarily related peptidases of the M23 family, lysostaphin and LytM. Through nuclear magnetic resonance, mass spectrometry, information-driven modelling, site-directed mutagenesis and biochemical approaches, we propose a model in which peptidoglycan cross-linking affects the activity, selectivity and specificity of these two structurally related enzymes differently.
Topics: Humans; Staphylococcus aureus; Peptidoglycan; Hydrolases; Lysostaphin; Mass Spectrometry; Staphylococcal Infections; Cell Wall
PubMed: 37872144
DOI: 10.1038/s41467-023-42506-w -
Sub-cellular Biochemistry 2019The Lpp lipoprotein of Escherichia coli is the first identified protein with a covalently linked lipid. It is chemically bound by its C-terminus to murein... (Review)
Review
The Lpp lipoprotein of Escherichia coli is the first identified protein with a covalently linked lipid. It is chemically bound by its C-terminus to murein (peptidoglycan) and inserts by the lipid at the N-terminus into the outer membrane. As the most abundant protein in E. coli (10 molecules per cell) it plays an important role for the integrity of the cell envelope. Lpp represents the type protein of a large variety of lipoproteins found in Gram-negative and Gram-positive bacteria and in archaea that have in common the lipid structure for anchoring the proteins to membranes but otherwise strongly vary in sequence, structure, and function. Predicted lipoproteins in known prokaryotic genomes comprise 2.7% of all proteins. Lipoproteins are modified by a unique phospholipid pathway and transferred from the cytoplasmic membrane into the outer membrane by a special system. They are involved in protein incorporation into the outer membrane, protein secretion across the cytoplasmic membrane, periplasm and outer membrane, signal transduction, conjugation, cell wall metabolism, antibiotic resistance, biofilm formation, and adhesion to host tissues. They are only found in bacteria and function as signal molecules for the innate immune system of vertebrates, where they cause inflammation and elicit innate and adaptive immune response through Toll-like receptors. This review discusses various aspects of Lpp and other lipoproteins of Gram-negative and Gram-positive bacteria and archaea.
Topics: Animals; Archaea; Bacteria; Bacterial Outer Membrane Proteins; Cell Membrane; Escherichia coli Proteins; Lipoproteins; Peptidoglycan
PubMed: 31214984
DOI: 10.1007/978-3-030-18768-2_3 -
Critical Reviews in Microbiology Nov 2020The spread of bacterial strains resistant to commonly used antibiotics urges the development of novel antibacterial compounds. Ideally, these novel antimicrobials should... (Review)
Review
The spread of bacterial strains resistant to commonly used antibiotics urges the development of novel antibacterial compounds. Ideally, these novel antimicrobials should be less prone to the development of resistance. Peptidoglycan-degrading enzymes are a promising class of compounds with a fundamentally different mode of action compared to traditionally used antibiotics. The difference in the mechanism of action implies differences both in the mechanisms of resistance and the chances of its emergence. To critically assess the potential of resistance development to peptidoglycan-degrading enzymes, we review the available evidence for the development of resistance to these enzymes , along with the known mechanisms of resistance to lysozyme, bacteriocins, autolysins, and phage endolysins. We conclude that genetic determinants of resistance to peptidoglycan-degrading enzymes are unlikely to readily emerge However, resistance to these enzymes would probably spread by the horizontal transfer between intrinsically resistant and susceptible species. Finally, we speculate that the higher cost of the therapeutics based on peptidoglycan degrading enzymes compared to classical antibiotics might result in less misuse, which in turn would lead to lower selective pressure, making these antibacterials less prone to resistance development.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriophages; Drug Resistance, Bacterial; Enzymes; Humans; Peptidoglycan
PubMed: 32985279
DOI: 10.1080/1040841X.2020.1825333 -
Journal of Bacteriology Mar 2023Most bacteria have cell wall peptidoglycan surrounding their plasma membranes. The essential cell wall provides a scaffold for the envelope, protection against turgor... (Review)
Review
Most bacteria have cell wall peptidoglycan surrounding their plasma membranes. The essential cell wall provides a scaffold for the envelope, protection against turgor pressure and is a proven drug target. Synthesis of the cell wall involves reactions that span cytoplasmic and periplasmic compartments. Bacteria carry out the last steps of cell wall synthesis along their plasma membrane. The plasma membrane in bacteria is heterogeneous and contains membrane compartments. Here, I outline findings that highlight the emerging notion that plasma membrane compartments and the cell wall peptidoglycan are functionally intertwined. I start by providing models of cell wall synthesis compartmentalization within the plasma membrane in mycobacteria, Escherichia coli, and Bacillus subtilis. Then, I revisit literature that supports a role for the plasma membrane and its lipids in modulating enzymatic reactions that synthesize cell wall precursors. I also elaborate on what is known about bacterial lateral organization of the plasma membrane and the mechanisms by which organization is established and maintained. Finally, I discuss the implications of cell wall partitioning in bacteria and highlight how targeting plasma membrane compartmentalization serves as a way to disrupt cell wall synthesis in diverse species.
Topics: Peptidoglycan; Feedback; Cell Membrane; Cell Wall; Bacteria; Escherichia coli
PubMed: 36794934
DOI: 10.1128/jb.00433-22 -
Microbiology Spectrum Jul 2019The mycobacterial cell envelope consists of a typical plasma membrane of lipid and protein surrounded by a complex cell wall composed of carbohydrate and lipid. In... (Review)
Review
The mycobacterial cell envelope consists of a typical plasma membrane of lipid and protein surrounded by a complex cell wall composed of carbohydrate and lipid. In pathogenic species, such as , an outermost "capsule" layer surrounds the cell wall. This wall embraces a fundamental, covalently linked "cell-wall skeleton" composed of peptidoglycan, solidly attached to arabinogalactan, whose penta-saccharide termini are esterified by very-long-chain fatty acids (mycolic acids). These fatty acids form the inner leaflet of an outer membrane, called the mycomembrane, whose outer leaflet consists of a great variety of non-covalently linked lipids and glycolipids. The thickness of the mycomembrane, which is similar to that of the plasma membrane, is surprising in view of the length of mycoloyl residues, suggesting dedicated conformations of these fatty acids. Finally, a periplasmic space also exists in mycobacteria, between the plasma membrane and the peptidoglycan. This article provides a comprehensive overview of this biologically important and structurally unique mycobacterial cell compartment.
Topics: Animals; Cell Membrane; Cell Wall; Fatty Acids; Galactans; Glycolipids; Humans; Mycobacterium tuberculosis; Peptidoglycan; Tuberculosis
PubMed: 31267927
DOI: 10.1128/microbiolspec.GPP3-0027-2018 -
Current Topics in Microbiology and... 2017Gram-positive organisms, including the pathogens Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis, have dynamic cell envelopes that mediate... (Review)
Review
Gram-positive organisms, including the pathogens Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis, have dynamic cell envelopes that mediate interactions with the environment and serve as the first line of defense against toxic molecules. Major components of the cell envelope include peptidoglycan (PG), which is a well-established target for antibiotics, teichoic acids (TAs), capsular polysaccharides (CPS), surface proteins, and phospholipids. These components can undergo modification to promote pathogenesis, decrease susceptibility to antibiotics and host immune defenses, and enhance survival in hostile environments. This chapter will cover the structure, biosynthesis, and important functions of major cell envelope components in gram-positive bacteria. Possible targets for new antimicrobials will be noted.
Topics: Bacterial Capsules; Biofilms; Cell Membrane; Cell Wall; Gram-Positive Bacteria; Immune Evasion; Lipopolysaccharides; Peptidoglycan; Teichoic Acids
PubMed: 26919863
DOI: 10.1007/82_2015_5021