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Trends in Microbiology Jan 2019Fluorescent amino acid analogs have proven to be useful tools for studying the dynamics of peptidoglycan metabolism. García-Heredia and colleagues showed that their...
Fluorescent amino acid analogs have proven to be useful tools for studying the dynamics of peptidoglycan metabolism. García-Heredia and colleagues showed that their route of incorporation differs depending on the adjunct fluorophore and applied this property to investigate mycobacterial peptidoglycan synthesis and remodeling with heightened granularity.
Topics: Mycobacterium; Peptidoglycan
PubMed: 30497920
DOI: 10.1016/j.tim.2018.11.006 -
Methods in Molecular Biology (Clifton,... 2017Most gene clusters encoding multiprotein complexes of the bacterial cell envelope, such as conjugation and secretion systems, Type IV pili, and flagella, bear a gene...
Most gene clusters encoding multiprotein complexes of the bacterial cell envelope, such as conjugation and secretion systems, Type IV pili, and flagella, bear a gene encoding an enzyme with peptidoglycan hydrolase activity. These enzymes are usually glycoside hydrolases that cleave the glycan chains of the peptidoglycan. Their activities are spatially controlled to avoid cell lysis and to create localized rearrangement of the cell wall. This is assured by interaction with the structural subunits of the apparatus. Here we describe protocols to test the peptidoglycan hydrolase activity of these proteins in vitro and in solution.
Topics: Enzyme Activation; Hydrolysis; N-Acetylmuramoyl-L-alanine Amidase; Nephelometry and Turbidimetry; Peptidoglycan; Staining and Labeling
PubMed: 28667610
DOI: 10.1007/978-1-4939-7033-9_12 -
Current Biology : CB Jul 2021Dynamics of cell elongation and septation are key determinants of bacterial morphogenesis. These processes are intimately linked to peptidoglycan synthesis performed by...
Dynamics of cell elongation and septation are key determinants of bacterial morphogenesis. These processes are intimately linked to peptidoglycan synthesis performed by macromolecular complexes called the elongasome and the divisome. In rod-shaped bacteria, cell elongation and septation, which are dissociated in time and space, have been well described. By contrast, in ovoid-shaped bacteria, the dynamics and relationships between these processes remain poorly understood because they are concomitant and confined to a nanometer-scale annular region at midcell. Here, we set up a metabolic peptidoglycan labeling approach using click chemistry to image peptidoglycan synthesis by single-molecule localization microscopy in the ovoid bacterium Streptococcus pneumoniae. Our nanoscale-resolution data reveal spatiotemporal features of peptidoglycan assembly and fate along the cell cycle and provide geometrical parameters that we used to construct a morphogenesis model of the ovoid cell. These analyses show that septal and peripheral peptidoglycan syntheses first occur within a single annular region that later separates in two concentric regions and that elongation persists after septation is completed. In addition, our data reveal that freshly synthesized peptidoglycan is remodeled all along the cell cycle. Altogether, our work provides evidence that septal peptidoglycan is synthesized from the beginning of the cell cycle and is constantly remodeled through cleavage and insertion of material at its periphery. The ovoid-cell morphogenesis would thus rely on the relative dynamics between peptidoglycan synthesis and cleavage rather than on the existence of two distinct successive phases of peripheral and septal synthesis.
Topics: Bacteria; Bacterial Proteins; Cell Cycle; Cell Division; Cell Wall; Peptidoglycan; Streptococcus pneumoniae
PubMed: 33989523
DOI: 10.1016/j.cub.2021.04.041 -
Chemical Communications (Cambridge,... Nov 2020The interaction between host immunity and bacterial cells plays a pivotal role in a variety of human diseases. The bacterial cell wall component peptidoglycan (PG) is... (Review)
Review
The interaction between host immunity and bacterial cells plays a pivotal role in a variety of human diseases. The bacterial cell wall component peptidoglycan (PG) is known to stimulate an immune response, which makes PG a distinctive recognition element for unveiling these complicated molecular interactions. Pattern recognition receptor (PRR) proteins are among the critical components of this system that initially recognize molecular patterns associated with microorganisms such as bacteria and fungi. These molecular patterns are mostly embedded in the bacterial or fungal cell wall structure and can be released and presented to the immune system in various situations. Nonetheless, detailed knowledge of this recognition is limited due to the diversity among the PG polymer and its fragments; the subsequent responses by multiple hosts add more complexity. Here, we discuss how our understanding of the role and molecular mechanisms of the well-studied PRR, the NOD-like receptors (NLRs), in the human immune system has evolved in recent years. We highlight the instances of other classes of proteins with similar behavior in the recognition of PG that have been identified in other microorganisms such as yeasts. These proteins are particularly interesting because a network of cellular interactions exists between human host cells, bacteria and yeast as a part of the normal human flora. To support our understanding of these interactions, we provide insight into the chemist's toolbox of peptidoglycan probes that aid in the investigations of the behaviors of these proteins and other biological contexts relevant to the sensing and recognition of peptidoglycan. The importance of these interactions in human health for the development of biomarkers and biotherapy is highlighted.
Topics: Animals; Biosensing Techniques; Host-Pathogen Interactions; Humans; Immunity; Peptidoglycan
PubMed: 33057506
DOI: 10.1039/d0cc02605k -
PLoS Pathogens Dec 2015
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International Journal of Medical... Feb 2015Most Eubacteria possess peptidoglycan (PGN) or murein that surrounds the cytoplasmic membrane. While on the one hand this PGN sacculus is a very protective shield that... (Review)
Review
Most Eubacteria possess peptidoglycan (PGN) or murein that surrounds the cytoplasmic membrane. While on the one hand this PGN sacculus is a very protective shield that provides resistance to the internal turgor and adverse effects of the environment, it serves on the other hand as a major pattern of recognition due to its unique structure. Eukaryotes harness this particular bacterial macromolecule to perceive (pathogenic) microorganisms and initiate their immune defence. PGN fragments are generated by bacteria as turnover products during bacterial cell wall growth and these fragments can be sensed by plants and animals to assess a potential bacterial threat. To increase the sensitivity the concentration of PGN fragments can be amplified by host hydrolytic enzymes such as lysozyme or amidase. But also bacteria themselves are able to perceive information about the state of their cell wall by sensing small soluble fragments released from its PGN, which eventually leads to the induction of antibiotic responses or cell differentiation. How PGN is sensed by bacteria, plants and animals, and how the antibacterial defence is modulated by PGN perception is the issue of this review.
Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Cell Wall; Host-Pathogen Interactions; Peptidoglycan; Plants; Receptors, Immunologic
PubMed: 25596887
DOI: 10.1016/j.ijmm.2014.12.019 -
Current Pharmaceutical Design 2017Exploring a new target for antibacterial drug discovery has gained much attention because of the emergence of Multidrug Resistance (MDR) strains of bacteria. To overcome... (Review)
Review
Exploring a new target for antibacterial drug discovery has gained much attention because of the emergence of Multidrug Resistance (MDR) strains of bacteria. To overcome this problem the development of novel antibacterial was considered as highest priority task and was one of the biggest challenge since multiple factors were involved. The bacterial peptidoglycan biosynthetic pathway has been well documented in the last few years and has been found to be imperative source for the development of novel antibacterial agents with high target specificity as they are essential for bacterial survival and have no homologs in humans. We have therefore reviewed the process of peptidoglycan biosynthesis which involves various steps like formation of UDP-Nacetylglucosamine (GlcNAc), UDP-N-acetylmuramic acid (MurNAc) and lipid intermediates (Lipid I and Lipid II) which are controlled by various enzymes like GlmS, GlmM, GlmU enzyme, followed by Mur Ligases (MurAMurF) and finally by MraY and MurG respectively. These four amide ligases MurC-MurF can be used as the source for the development of novel multi-target antibacterial agents as they shared and conserved amino acid regions, catalytic mechanisms and structural features. This review begins with the need for novel antibacterial agents and challenges in their development even after the development of bacterial genomic studies. An overview of the peptidoglycan monomer formation, as a source of disparity in this process is presented, followed by detailed discussion of structural and functional aspects of all Mur enzymes and different chemical classes of their inhibitors along with their SAR studies and inhibitory potential. This review finally emphasizes on different patents and novel Mur inhibitors in the development phase.
Topics: Anti-Bacterial Agents; Drug Discovery; Enzyme Inhibitors; Ligases; Peptidoglycan
PubMed: 28201974
DOI: 10.2174/1381612823666170214115048 -
Microbial Cell Factories Aug 2014The cell wall of Gram-positive bacteria is a complex assemblage of glycopolymers and proteins. It consists of a thick peptidoglycan sacculus that surrounds the... (Review)
Review
The cell wall of Gram-positive bacteria is a complex assemblage of glycopolymers and proteins. It consists of a thick peptidoglycan sacculus that surrounds the cytoplasmic membrane and that is decorated with teichoic acids, polysaccharides, and proteins. It plays a major role in bacterial physiology since it maintains cell shape and integrity during growth and division; in addition, it acts as the interface between the bacterium and its environment. Lactic acid bacteria (LAB) are traditionally and widely used to ferment food, and they are also the subject of more and more research because of their potential health-related benefits. It is now recognized that understanding the composition, structure, and properties of LAB cell walls is a crucial part of developing technological and health applications using these bacteria. In this review, we examine the different components of the Gram-positive cell wall: peptidoglycan, teichoic acids, polysaccharides, and proteins. We present recent findings regarding the structure and function of these complex compounds, results that have emerged thanks to the tandem development of structural analysis and whole genome sequencing. Although general structures and biosynthesis pathways are conserved among Gram-positive bacteria, studies have revealed that LAB cell walls demonstrate unique properties; these studies have yielded some notable, fundamental, and novel findings. Given the potential of this research to contribute to future applied strategies, in our discussion of the role played by cell wall components in LAB physiology, we pay special attention to the mechanisms controlling bacterial autolysis, bacterial sensitivity to bacteriophages and the mechanisms underlying interactions between probiotic bacteria and their hosts.
Topics: Acetylation; Bacterial Proteins; Cell Wall; Host-Pathogen Interactions; Lactobacillaceae; Lipopolysaccharides; Peptidoglycan; Polysaccharides, Bacterial; Teichoic Acids
PubMed: 25186919
DOI: 10.1186/1475-2859-13-S1-S9 -
Sub-cellular Biochemistry 2019The bacterial cell wall is the validated target of mainstream antimicrobials such as penicillin and vancomycin. Penicillin and other β-lactams act by targeting... (Review)
Review
The bacterial cell wall is the validated target of mainstream antimicrobials such as penicillin and vancomycin. Penicillin and other β-lactams act by targeting Penicillin-Binding Proteins (PBPs), enzymes that play key roles in the biosynthesis of the main component of the cell wall, the peptidoglycan. Despite the spread of resistance towards these drugs, the bacterial cell wall continues to be a major Achilles' heel for microbial survival, and the exploration of the cell wall formation machinery is a vast field of work that can lead to the development of novel exciting therapies. The sheer complexity of the cell wall formation process, however, has created a significant challenge for the study of the macromolecular interactions that regulate peptidoglycan biosynthesis. New developments in genetic and biochemical screens, as well as different aspects of structural biology, have shed new light on the importance of complexes formed by PBPs, notably within the cell wall elongation machinery. This chapter summarizes structural and functional details of PBP complexes involved in the periplasmic and membrane steps of peptidoglycan biosynthesis with a focus on cell wall elongation. These assemblies could represent interesting new targets for the eventual development of original antibacterials.
Topics: Bacteria; Cell Wall; Penicillin-Binding Proteins; Peptidoglycan
PubMed: 31939154
DOI: 10.1007/978-3-030-28151-9_8 -
PLoS Pathogens Dec 2015Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a... (Review)
Review
Nearly all bacteria contain a peptidoglycan cell wall. The peptidoglycan precursor molecule is LipidII, containing the basic peptidoglycan building block attached to a lipid. Although the suitability of LipidII as an antibacterial target has long been recognized, progress on elucidating the role(s) of LipidII in bacterial cell biology has been slow. The focus of this review is on exciting new developments, both with respect to antibacterials targeting LipidII as well as the emerging role of LipidII in organizing the membrane and cell wall synthesis. It appears that on both sides of the membrane, LipidII plays crucial roles in organizing cytoskeletal proteins and peptidoglycan synthesis machineries. Finally, the recent discovery of no less than three different categories of LipidII flippases will be discussed.
Topics: Bacterial Proteins; Cell Wall; Peptidoglycan
PubMed: 26679002
DOI: 10.1371/journal.ppat.1005213