-
Microbiology Spectrum Jul 2019Dating back to the 1960s, initial studies on the staphylococcal cell wall were driven by the need to clarify the mode of action of the first antibiotics and the... (Review)
Review
Dating back to the 1960s, initial studies on the staphylococcal cell wall were driven by the need to clarify the mode of action of the first antibiotics and the resistance mechanisms developed by the bacteria. During the following decades, the elucidation of the biosynthetic path and primary composition of staphylococcal cell walls was propelled by advances in microbial cell biology, specifically, the introduction of high-resolution analytical techniques and molecular genetic approaches. The field of staphylococcal cell wall gradually gained its own significance as the complexity of its chemical structure and involvement in numerous cellular processes became evident, namely its versatile role in host interactions, coordination of cell division and environmental stress signaling.This chapter includes an updated description of the anatomy of staphylococcal cell walls, paying particular attention to information from the last decade, under four headings: high-resolution analysis of the peptidoglycan; variations in peptidoglycan composition; genetic determinants and enzymes in cell wall synthesis; and complex functions of cell walls. The latest contributions to a more precise picture of the staphylococcal cell envelope were possible due to recently developed state-of-the-art microscopy and spectroscopy techniques and to a wide combination of -omics approaches, that are allowing to obtain a more integrative view of this highly dynamic structure.
Topics: Animals; Cell Membrane; Cell Wall; Humans; Peptidoglycan; Staphylococcal Infections; Staphylococcus aureus
PubMed: 31322105
DOI: 10.1128/microbiolspec.GPP3-0068-2019 -
Trends in Microbiology Jul 2019Peptidoglycan (PG) is a ubiquitous structural polysaccharide of the bacterial cell wall, essential in preserving cell integrity by withstanding turgor pressure. Any... (Review)
Review
Peptidoglycan (PG) is a ubiquitous structural polysaccharide of the bacterial cell wall, essential in preserving cell integrity by withstanding turgor pressure. Any change that affects its biosynthesis or degradation will disturb cell viability, therefore PG is one of the main targets of antimicrobial drugs. Considering its major role in cell structure and integrity, the study of PG is of utmost relevance, with prospective ramifications to several disciplines such as microbiology, pharmacology, agriculture, and pathogenesis. Traditionally, high-performance liquid chromatography (HPLC) has been the workhorse of PG analysis. In recent years, technological and bioinformatic developments have upgraded this seminal technique, making analysis more sensitive and efficient than ever before. Here we describe a set of analytical tools for the study of PG structure (from composition to 3D architecture), identify the most recent trends, and discuss future challenges in the field.
Topics: Amino Acids; Models, Molecular; Molecular Structure; N-Acetylmuramoyl-L-alanine Amidase; Peptidoglycan; Polysaccharides, Bacterial
PubMed: 30833206
DOI: 10.1016/j.tim.2019.01.009 -
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 -
Phytochemistry Jul 2020Peptidoglycan has been retained in chloroplasts that have evolved from cyanobacteria along some evolutionary tracks, but has seemingly been quickly eliminated during... (Review)
Review
Peptidoglycan has been retained in chloroplasts that have evolved from cyanobacteria along some evolutionary tracks, but has seemingly been quickly eliminated during evolution of others. It has been eliminated in Rhodophyta, Chlorophyta, Pteridophyta and Spermatophyta, but has been retained in streptophyte algae, Glaukophyta, and Lycophyta. In this article questions emerging from this are raised, and for some of them answers are suggested.
Topics: Cell Wall; Chlorophyta; Chloroplasts; Eukaryota; Peptidoglycan; Phylogeny
PubMed: 32289597
DOI: 10.1016/j.phytochem.2020.112370 -
Cold Spring Harbor Perspectives in... Mar 2015The mycobacterial bacillus is encompassed by a remarkably elaborate cell wall structure. The mycolyl-arabinogalactan-peptidoglycan (mAGP) complex is essential for the... (Review)
Review
The mycobacterial bacillus is encompassed by a remarkably elaborate cell wall structure. The mycolyl-arabinogalactan-peptidoglycan (mAGP) complex is essential for the viability of Mycobacterium tuberculosis and maintains a robust basal structure supporting the upper "myco-membrane." M. tuberculosis peptidoglycan, although appearing to be unexceptional at first glance, contains a number of unique molecular subtleties that become particularly important as the TB-bacilli enters into nonreplicative growth during dormancy. Arabinogalactan, a highly branched polysaccharide, serves to connect peptidoglycan with the outer mycolic acid layer, and a variety of unique glycolsyltransferases are used for its assembly. In this review, we shall explore the microbial chemistry of this unique heteropolysacchride, examine the molecular genetics that underpins its fabrication, and discuss how the essential biosynthetic process might be exploited for the development of future anti-TB chemotherapies.
Topics: Cell Wall; Galactans; Humans; Mycobacterium tuberculosis; Peptidoglycan; Sensitivity and Specificity; Virulence
PubMed: 25818664
DOI: 10.1101/cshperspect.a021113 -
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 -
Journal of Bacteriology Mar 2023The dynamic composition of the peptidoglycan cell wall has been the subject of intense research for decades, yet how bacteria coordinate the synthesis of new... (Review)
Review
The dynamic composition of the peptidoglycan cell wall has been the subject of intense research for decades, yet how bacteria coordinate the synthesis of new peptidoglycan with the turnover and remodeling of existing peptidoglycan remains elusive. Diversity and redundancy within peptidoglycan synthases and peptidoglycan autolysins, enzymes that degrade peptidoglycan, have often made it challenging to assign physiological roles to individual enzymes and determine how those activities are regulated. For these reasons, peptidoglycan glycosidases, which cleave within the glycan strands of peptidoglycan, have proven veritable masters of misdirection over the years. Unlike many of the broadly conserved peptidoglycan synthetic complexes, diverse bacteria can employ unrelated glycosidases to achieve the same physiological outcome. Additionally, although the mechanisms of action for many individual enzymes have been characterized, apparent conserved homologs in other organisms can exhibit an entirely different biochemistry. This flexibility has been recently demonstrated in the context of three functions critical to vegetative growth: (i) release of newly synthesized peptidoglycan strands from their membrane anchors, (ii) processing of peptidoglycan turned over during cell wall expansion, and (iii) removal of peptidoglycan fragments that interfere with daughter cell separation during cell division. Finally, the regulation of glycosidase activity during these cell processes may be a cumulation of many factors, including protein-protein interactions, intrinsic substrate preferences, substrate availability, and subcellular localization. Understanding the true scope of peptidoglycan glycosidase activity will require the exploration of enzymes from diverse organisms with equally diverse growth and division strategies.
Topics: Glycoside Hydrolases; Peptidoglycan; Bacteria; Cell Wall; Cell Division; Bacterial Proteins
PubMed: 36757204
DOI: 10.1128/jb.00428-22 -
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 -
Annual Review of Microbiology 2015Mycobacterium tuberculosis remains one of the most successful bacterial pathogens, claiming over 1.3 million lives worldwide in 2013. The emergence of... (Review)
Review
Mycobacterium tuberculosis remains one of the most successful bacterial pathogens, claiming over 1.3 million lives worldwide in 2013. The emergence of multidrug-resistant and extensively drug-resistant isolates has prompted the need for new drugs and drug targets. M. tuberculosis possesses an unusual cell wall dominated by lipids and carbohydrates that provides a permeability barrier against hydrophilic drugs and is crucial for its survival and virulence. This large macromolecular structure, termed the mycolyl-arabinogalactan-peptidoglycan complex, and the phosphatidyl-myo-inositol-based lipoglycans are key features of the mycobacterial cell wall. Assembly of these cell wall components is an attractive target for the development of chemotherapeutics against tuberculosis. Herein, we focus on recent biochemical and molecular insights into these complex molecules of M. tuberculosis cell wall.
Topics: Cell Wall; Galactans; Mycobacterium tuberculosis; Mycolic Acids; Peptidoglycan; Polysaccharides, Bacterial
PubMed: 26488279
DOI: 10.1146/annurev-micro-091014-104121 -
ELife Feb 2021Many antibiotics target the assembly of cell wall peptidoglycan, an essential, heteropolymeric mesh that encases most bacteria. In rod-shaped bacteria, cell wall...
Many antibiotics target the assembly of cell wall peptidoglycan, an essential, heteropolymeric mesh that encases most bacteria. In rod-shaped bacteria, cell wall elongation is spatially precise yet relies on limited pools of lipid-linked precursors that generate and are attracted to membrane disorder. By tracking enzymes, substrates, and products of peptidoglycan biosynthesis in , we show that precursors are made in plasma membrane domains that are laterally and biochemically distinct from sites of cell wall assembly. Membrane partitioning likely contributes to robust, orderly peptidoglycan synthesis, suggesting that these domains help template peptidoglycan synthesis. The cell wall-organizing protein DivIVA and the cell wall itself promote domain homeostasis. These data support a model in which the peptidoglycan polymer feeds back on its membrane template to maintain an environment conducive to directional synthesis. Our findings are applicable to rod-shaped bacteria that are phylogenetically distant from , indicating that horizontal compartmentalization of precursors may be a general feature of bacillary cell wall biogenesis.
Topics: Cell Cycle; Cell Membrane; Cell Wall; Mycobacterium smegmatis; Peptidoglycan
PubMed: 33544079
DOI: 10.7554/eLife.60263