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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 -
FEMS Microbiology Reviews Mar 2008The peptidoglycan (murein) sacculus is a unique and essential structural element in the cell wall of most bacteria. Made of glycan strands cross-linked by short... (Review)
Review
The peptidoglycan (murein) sacculus is a unique and essential structural element in the cell wall of most bacteria. Made of glycan strands cross-linked by short peptides, the sacculus forms a closed, bag-shaped structure surrounding the cytoplasmic membrane. There is a high diversity in the composition and sequence of the peptides in the peptidoglycan from different species. Furthermore, in several species examined, the fine structure of the peptidoglycan significantly varies with the growth conditions. Limited number of biophysical data on the thickness, elasticity and porosity of peptidoglycan are available. The different models for the architecture of peptidoglycan are discussed with respect to structural and physical parameters.
Topics: Bacteria; Cell Wall; Escherichia coli; Models, Molecular; Molecular Structure; Peptidoglycan
PubMed: 18194336
DOI: 10.1111/j.1574-6976.2007.00094.x -
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 -
Nature Reviews. Immunology Apr 2018The innate immune system recognizes microbial products using germline-encoded receptors that initiate inflammatory responses to infection. The bacterial cell wall... (Review)
Review
The innate immune system recognizes microbial products using germline-encoded receptors that initiate inflammatory responses to infection. The bacterial cell wall component peptidoglycan is a prime example of a conserved pathogen-associated molecular pattern (PAMP) for which the innate immune system has evolved sensing mechanisms. Peptidoglycan is a direct target for innate immune receptors and also regulates the accessibility of other PAMPs to additional innate immune receptors. Subtle structural modifications to peptidoglycan can influence the ability of the innate immune system to detect bacteria and can allow bacteria to evade or alter host defences. This Review focuses on the mechanisms of peptidoglycan recognition that are used by mammalian cells and discusses new insights into the role of peptidoglycan recognition in inflammation, metabolism, immune homeostasis and disease.
Topics: Animals; Carrier Proteins; Gastrointestinal Microbiome; Humans; Immunity, Innate; Immunity, Mucosal; Models, Immunological; NLR Proteins; Peptidoglycan; Receptors, Cell Surface; Signal Transduction; Toll-Like Receptors
PubMed: 29292393
DOI: 10.1038/nri.2017.136 -
Glycoconjugate Journal Oct 2018Peptidoglycan, a major glycoconjugate in the mycobacterial cell envelope provides strength to resist osmotic stress and plays a pivotal role in maintaining the cellular... (Review)
Review
Peptidoglycan, a major glycoconjugate in the mycobacterial cell envelope provides strength to resist osmotic stress and plays a pivotal role in maintaining the cellular morphology. Several unique growth stage specific structural alterations occur in its constituent monosaccharides and peptides that allow Mycobacterium to survive nutrient starvation and environmental stress. Here, we discuss the enzymes involved in its intricate biosynthesis that are novel targets for therapeutic intervention and provide an opportunity for potential antibiotic adjuvants. We also revisit the enzymatic steps which are critical for maintaining the equilibrium between peptidoglycan synthesis and hydrolysis during cellular growth and division specifically focused on the importance of cell wall remodelling during "exit from dormancy" in Mycobacterium, a phenomenon with tremendous physiological and therapeutic importance for intervention in mycobacterial infections.
Topics: Cell Division; Cell Membrane; Cell Membrane Permeability; Drug Delivery Systems; Mycobacterium; Peptidoglycan
PubMed: 30232572
DOI: 10.1007/s10719-018-9842-7 -
FEMS Microbiology Reviews Jan 2021Microbiota, and the plethora of signalling molecules that they generate, are a major driving force that underlies a striking range of inter-individual physioanatomic and... (Review)
Review
Microbiota, and the plethora of signalling molecules that they generate, are a major driving force that underlies a striking range of inter-individual physioanatomic and behavioural consequences for the host organism. Among the bacterial effectors, one finds peptidoglycan, the major constituent of the bacterial cell surface. In the steady-state, fragments of peptidoglycan are constitutively liberated from bacterial members of the gut microbiota, cross the gut epithelial barrier and enter the host system. The fate of these peptidoglycan fragments, and the outcome for the host, depends on the molecular nature of the peptidoglycan, as well the cellular profile of the recipient tissue, mechanism of cell entry, the expression of specific processing and recognition mechanisms by the cell, and the local immune context. At the target level, physiological processes modulated by peptidoglycan are extremely diverse, ranging from immune activation to small molecule metabolism, autophagy and apoptosis. In this review, we bring together a fragmented body of literature on the kinetics and dynamics of peptidoglycan interactions with the mammalian host, explaining how peptidoglycan functions as a signalling molecule in the host under physiological conditions, how it disseminates within the host, and the cellular responses to peptidoglycan.
Topics: Animals; Bacteria; Host-Pathogen Interactions; Humans; Mammals; Peptidoglycan; Signal Transduction
PubMed: 32897324
DOI: 10.1093/femsre/fuaa044 -
PLoS Pathogens Dec 2015
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Methods in Molecular Biology (Clifton,... 2019The composition of Neisseria peptidoglycan has been of scientific interest for over four decades. Initial investigations focused on discovering the mechanisms causing...
The composition of Neisseria peptidoglycan has been of scientific interest for over four decades. Initial investigations focused on discovering the mechanisms causing rising rates of antibiotic resistance in N. gonorrhoeae by determining differences in peptidoglycan composition in penicillin susceptible and resistant strains. The discovery that cytotoxic peptidoglycan fragments are also released by Neisseria furthered the interest in peptidoglycan composition. This method describes the purification, enzymatic degradation, and separation of peptidoglycan fragments by high-performance liquid chromatography (HPLC). It also describes the preparation of samples so that they can be positively identified by mass spectrometry.
Topics: Bacterial Proteins; Cell Wall; Chromatography, High Pressure Liquid; Mass Spectrometry; Neisseria gonorrhoeae; Peptidoglycan
PubMed: 31119621
DOI: 10.1007/978-1-4939-9496-0_8 -
Microbiology and Molecular Biology... Dec 2018The clinical and epidemiological threat of the growing antimicrobial resistance in Gram-negative pathogens, particularly for β-lactams, the most frequently used and... (Review)
Review
The clinical and epidemiological threat of the growing antimicrobial resistance in Gram-negative pathogens, particularly for β-lactams, the most frequently used and relevant antibiotics, urges research to find new therapeutic weapons to combat the infections caused by these microorganisms. An essential previous step in the development of these therapeutic solutions is to identify their potential targets in the biology of the pathogen. This is precisely what we sought to do in this review specifically regarding the barely exploited field analyzing the interplay among the biology of the peptidoglycan and related processes, such as β-lactamase regulation and virulence. Hence, here we gather, analyze, and integrate the knowledge derived from published works that provide information on the topic, starting with those dealing with the historically neglected essential role of the Gram-negative peptidoglycan in virulence, including structural, biogenesis, remodeling, and recycling aspects, in addition to proinflammatory and other interactions with the host. We also review the complex link between intrinsic β-lactamase production and peptidoglycan metabolism, as well as the biological costs potentially associated with the expression of horizontally acquired β-lactamases. Finally, we analyze the existing evidence from multiple perspectives to provide useful clues for identifying targets enabling the future development of therapeutic options attacking the peptidoglycan-virulence interconnection as a key weak point of the Gram-negative pathogens to be used, if not to kill the bacteria, to mitigate their capacity to produce severe infections.
Topics: Animals; Anti-Bacterial Agents; Cell Wall; Gram-Negative Bacteria; Host-Pathogen Interactions; Humans; Mice; Mice, Knockout; Peptidoglycan; Virulence; beta-Lactamases
PubMed: 30209071
DOI: 10.1128/MMBR.00033-18 -
Developmental and Comparative Immunology Jan 2014Innate immunity is the front line of self-defense against infectious non-self in vertebrates and invertebrates. The innate immune system is mediated by germ-line... (Review)
Review
Innate immunity is the front line of self-defense against infectious non-self in vertebrates and invertebrates. The innate immune system is mediated by germ-line encoding pattern recognition molecules (pathogen sensors) that recognize conserved molecular patterns present in the pathogens but absent in the host. Peptidoglycans (PGN) are essential cell wall components of almost all bacteria, except mycoplasma lacking a cell wall, which provides the host immune system an advantage for detecting invading bacteria. Several families of pattern recognition molecules that detect PGN and PGN-derived compounds have been indentified, and the role of PGRP family members in host defense is relatively well-characterized in Drosophila. This review focuses on the role of PGRP family members in the recognition of invading bacteria and the activation and modulation of immune responses in Drosophila.
Topics: Animals; Bacterial Infections; Cell Wall; Drosophila Proteins; Drosophila melanogaster; Host-Pathogen Interactions; Humans; Immunity, Innate; Peptidoglycan; Receptors, Pattern Recognition
PubMed: 23796791
DOI: 10.1016/j.dci.2013.06.006