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Current Opinion in Microbiology Feb 2015Mycobacterium tuberculosis contributed to the discovery of delayed-type hypersensitivity and cell-mediated immunity. However, the biochemical basis for the... (Review)
Review
PURPOSE
Mycobacterium tuberculosis contributed to the discovery of delayed-type hypersensitivity and cell-mediated immunity. However, the biochemical basis for the immunogenicity of the mycobacterial cell wall has until recently remained unknown.
RECENT FINDINGS
Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) responds to bacterial peptidolycan-derived muramyl dipeptide (MDP). Whereas most bacteria produce N-acetyl MDP, mycobacteria produce an unusual modified form of MDP, called N-glycolyl MDP. Disruption of N-glycolyl MDP synthesis in mycobacteria greatly diminishes the contribution of NOD2 to mycobacterial sensing. Additionally, N-glycolyl MDP is more potent and efficacious than N-acetyl MDP at inducing innate responses and T cell-mediated immunity.
SUMMARY
The sensitivity of NOD2 to the mycobacterial peptidoglycan may link the natural history of both innate and adaptive immunity to mycobacterial infection.
Topics: Acetylmuramyl-Alanyl-Isoglutamine; Cell Wall; Freund's Adjuvant; Immunity, Innate; Mycobacterium tuberculosis; Nod2 Signaling Adaptor Protein; Peptidoglycan; T-Lymphocytes
PubMed: 25483349
DOI: 10.1016/j.mib.2014.11.015 -
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 -
ELife Oct 2018A better understanding of the mechanisms underpinning the growth of mycobacteria could help identify targets for new antibiotics.
A better understanding of the mechanisms underpinning the growth of mycobacteria could help identify targets for new antibiotics.
Topics: Cell Wall; Mycobacterium tuberculosis; Peptidoglycan
PubMed: 30355443
DOI: 10.7554/eLife.42033 -
Journal of Agricultural and Food... Sep 2022Lysostaphin is a potent bacteriolytic enzyme with endopeptidase activity against the common pathogen . By digesting the pentaglycine crossbridge in the cell wall... (Review)
Review
Lysostaphin is a potent bacteriolytic enzyme with endopeptidase activity against the common pathogen . By digesting the pentaglycine crossbridge in the cell wall peptidoglycan of including the methicillin-resistant strains, lysostaphin initiates rapid lysis of planktonic and sessile cells (biofilms) and has great potential for use in agriculture, food industries, and pharmaceutical industries. In the past few decades, there have been tremendous efforts in potentiating lysostaphin for better applications in these fields, including engineering of the enzyme for higher potency and lower immunogenicity with longer-lasting effects, formulation and immobilization of the enzyme for higher stability and better durability, and recombinant expression for low-cost industrial production and biocontrol. These achievements are extensively reviewed in this article focusing on applications in disease control, food preservation, surface decontamination, and pathogen detection. In addition, some basic properties of lysostaphin that have been controversial and only elucidated recently are summarized, including the substrate-binding properties, the number of zinc-binding sites, the substrate range, and the cleavage site in the pentaglycine crossbridge. Resistance to lysostaphin is also highlighted with a focus on various mechanisms. This article is concluded with a discussion on the limitations and future perspectives for the actual applications of lysostaphin.
Topics: Anti-Bacterial Agents; Bacteriolysis; Lysostaphin; Peptidoglycan; Staphylococcus aureus; Zinc
PubMed: 36082619
DOI: 10.1021/acs.jafc.2c03459 -
Current Opinion in Immunology Feb 2016Gram-negative bacteria represent a major group of pathogens that infect all eukaryotes from plants to mammals. Gram-negative microbe-associated molecular patterns... (Review)
Review
Gram-negative bacteria represent a major group of pathogens that infect all eukaryotes from plants to mammals. Gram-negative microbe-associated molecular patterns include lipopolysaccharides and peptidoglycans, major immunostimulatory determinants across phyla. Recent advances have furthered our understanding of Gram-negative detection beyond the well-defined pattern recognition receptors such as TLR4. A B-type lectin receptor for LPS and Lysine-motif containing receptors for peptidoglycans were recently added to the plant arsenal. Caspases join the ranks of mammalian cytosolic immune detectors by binding LPS, and make TLR4 redundant for septic shock. Fascinating bacterial evasion mechanisms lure the host into tolerance or promote inter-bacterial competition. Our review aims to cover recent advances on bacterial messages and host decoding systems across phyla, and highlight evolutionarily recurrent strategies.
Topics: Animals; Caspases; Gene Expression Regulation; Gram-Negative Bacteria; Humans; Immune Evasion; Immunity, Innate; Lipopolysaccharides; Peptidoglycan; Phylogeny; Plants; Receptors, Cell Surface; Receptors, Mitogen; Signal Transduction; Species Specificity; Toll-Like Receptor 4
PubMed: 26569344
DOI: 10.1016/j.coi.2015.10.007 -
Current Opinion in Microbiology Apr 2023Most bacteria are surrounded by a cell wall composed of peptidoglycan (PG) that specifies shape and protects the cell from osmotic rupture. Growth, division, and... (Review)
Review
Most bacteria are surrounded by a cell wall composed of peptidoglycan (PG) that specifies shape and protects the cell from osmotic rupture. Growth, division, and morphogenesis are intimately linked to the synthesis of this exoskeleton but also its hydrolysis. The enzymes that cleave the PG meshwork require careful control to prevent aberrant hydrolysis and loss of envelope integrity. Bacteria employ diverse mechanisms to control the activity, localization, and abundance of these potentially autolytic enzymes. Here, we discuss four examples of how cells integrate these control mechanisms to finely tune cell wall hydrolysis. We highlight recent advances and exciting avenues for future investigation.
Topics: Peptidoglycan; N-Acetylmuramoyl-L-alanine Amidase; Bacteria; Cell Wall; Bacterial Proteins
PubMed: 36812681
DOI: 10.1016/j.mib.2023.102279 -
Methods in Molecular Biology (Clifton,... 2024Most bacterial secretion systems are large machines that cross the cell envelope to deliver effectors outside the cell or directly into target cells. The peptidoglycan...
Most bacterial secretion systems are large machines that cross the cell envelope to deliver effectors outside the cell or directly into target cells. The peptidoglycan layer can therefore represent a physical barrier for the assembly of these large machines. Secretion systems and their counterparts such as type IV pili, flagella, and conjugation machines have therefore evolved or hijacked enzymes with peptidoglycan degradation 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 local rearrangement of the cell wall. In addition, peptidoglycan hydrolases may not be only required for the proper assembly of the secretion systems but may directly participate to the release of the effectors. Finally, several antibacterial effectors possess peptidoglycan degradation activity that damage the cell wall once delivered in the target cell. Here, we describe protocols to test the peptidoglycan degradation activity of these proteins in vitro and in solution.
Topics: Peptidoglycan; Anti-Bacterial Agents; Bacterial Secretion Systems; Cell Death; Cell Membrane
PubMed: 37930529
DOI: 10.1007/978-1-0716-3445-5_12 -
Parasitology Feb 2018Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB), is recognized as a global health emergency as promoted by the World Health Organization.... (Review)
Review
Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB), is recognized as a global health emergency as promoted by the World Health Organization. Over 1 million deaths per year, along with the emergence of multi- and extensively-drug resistant strains of Mtb, have triggered intensive research into the pathogenicity and biochemistry of this microorganism, guiding the development of anti-TB chemotherapeutic agents. The essential mycobacterial cell wall, sharing some common features with all bacteria, represents an apparent 'Achilles heel' that has been targeted by TB chemotherapy since the advent of TB treatment. This complex structure composed of three distinct layers, peptidoglycan, arabinogalactan and mycolic acids, is vital in supporting cell growth, virulence and providing a barrier to antibiotics. The fundamental nature of cell wall synthesis and assembly has rendered the mycobacterial cell wall as the most widely exploited target of anti-TB drugs. This review provides an overview of the biosynthesis of the prominent cell wall components, highlighting the inhibitory mechanisms of existing clinical drugs and illustrating the potential of other unexploited enzymes as future drug targets.
Topics: Anti-Bacterial Agents; Cell Wall; Drug Delivery Systems; Drug Design; Galactans; Humans; Mycobacterium tuberculosis; Mycolic Acids; Peptidoglycan; Tuberculosis; Virulence
PubMed: 27976597
DOI: 10.1017/S0031182016002377 -
Frontiers in Cellular and Infection... 2023Most bacteria divide through a highly conserved process called binary fission, in which there is symmetric growth of daughter cells and the synthesis of peptidoglycan at... (Review)
Review
Most bacteria divide through a highly conserved process called binary fission, in which there is symmetric growth of daughter cells and the synthesis of peptidoglycan at the mid-cell to enable cytokinesis. During this process, the parental cell replicates its chromosomal DNA and segregates replicated chromosomes into the daughter cells. The mechanisms that regulate binary fission have been extensively studied in several model organisms, including , and . These analyses have revealed that a multi-protein complex called the divisome forms at the mid-cell to enable peptidoglycan synthesis and septation during division. In addition, rod-shaped bacteria form a multi-protein complex called the elongasome that drives sidewall peptidoglycan synthesis necessary for the maintenance of rod shape and the lengthening of the cell prior to division. In adapting to their intracellular niche, the obligate intracellular bacteria discussed here have eliminated one to several of the divisome gene products essential for binary fission in . In addition, genes that encode components of the elongasome, which were mostly lost as rod-shaped bacteria evolved into coccoid organisms, have been retained during the reductive evolutionary process that some coccoid obligate intracellular bacteria have undergone. Although the precise molecular mechanisms that regulate the division of obligate intracellular bacteria remain undefined, the studies summarized here indicate that obligate intracellular bacteria exhibit remarkable plasticity in their cell division processes.
Topics: Escherichia coli; Peptidoglycan; Bacterial Proteins; Cell Division; Cytokinesis
PubMed: 37876871
DOI: 10.3389/fcimb.2023.1205488 -
Proceedings of the National Academy of... Oct 2023Bacteria produce a structural layer of peptidoglycan (PG) that enforces cell shape, resists turgor pressure, and protects the cell. As bacteria grow and divide, the...
Bacteria produce a structural layer of peptidoglycan (PG) that enforces cell shape, resists turgor pressure, and protects the cell. As bacteria grow and divide, the existing layer of PG is remodeled and PG fragments are released. Enterics such as go to great lengths to internalize and reutilize PG fragments. is estimated to break down one-third of its cell wall, yet only loses ~0 to 5% of meso-diaminopimelic acid, a PG-specific amino acid, per generation. Two transporters were identified early on to possibly be the primary permease that facilitates PG fragment recycling, i) AmpG and ii) the Opp ATP binding cassette transporter in conjunction with a PG-specific periplasmic binding protein, MppA. The contribution of each transporter to PG recycling has been debated. Here, we have found that AmpG and MppA/Opp are differentially regulated by carbon source and growth phase. In addition, MppA/Opp is uniquely capable of high-affinity scavenging of muropeptides from growth media, demonstrating that AmpG and MppA/Opp allow for different strategies of recycling PG fragments. Altogether, this work clarifies environmental contexts under which utilizes distinct permeases for PG recycling and explores how scavenging by MppA/Opp could be beneficial in mixed communities.
Topics: Membrane Transport Proteins; Escherichia coli; Peptidoglycan; Bacterial Proteins; Bacteria; Cell Wall
PubMed: 37871219
DOI: 10.1073/pnas.2308940120