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Molecular Microbiology May 2008Bacteria retain certain proteins at their cell envelopes by attaching them in a non-covalent manner to peptidoglycan, using specific protein domains, such as the... (Review)
Review
Bacteria retain certain proteins at their cell envelopes by attaching them in a non-covalent manner to peptidoglycan, using specific protein domains, such as the prominent LysM (Lysin Motif) domain. More than 4000 (Pfam PF01476) proteins of both prokaryotes and eukaryotes have been found to contain one or more Lysin Motifs. Notably, this collection contains not only truly secreted proteins, but also (outer-)membrane proteins, lipoproteins or proteins bound to the cell wall in a (non-)covalent manner. The motif typically ranges in length from 44 to 65 amino acid residues and binds to various types of peptidoglycan and chitin, most likely recognizing the N-acetylglucosamine moiety. Most bacterial LysM-containing proteins are peptidoglycan hydrolases with various cleavage specificities. Binding of certain LysM proteins to cells of Gram-positive bacteria has been shown to occur at specific sites, as binding elsewhere is hindered by the presence of other cell wall components such as lipoteichoic acids. Interestingly, LysM domains of certain plant kinases enable the plant to recognize its symbiotic bacteria or sense and induce resistance against fungi. This interaction is triggered by chitin-like compounds that are secreted by the symbiotic bacteria or released from fungi, demonstrating an important sensing function of LysMs.
Topics: Acetylglucosamine; Amino Acid Motifs; Animals; Bacterial Proteins; Consensus Sequence; Evolution, Molecular; Peptidoglycan; Protein Structure, Tertiary; Proteins; Repetitive Sequences, Amino Acid; Substrate Specificity
PubMed: 18430080
DOI: 10.1111/j.1365-2958.2008.06211.x -
Cells Feb 2023Plastids in plants are assumed to have evolved from cyanobacteria as they have maintained several bacterial features. Recently, peptidoglycans, as bacterial cell wall...
Plastids in plants are assumed to have evolved from cyanobacteria as they have maintained several bacterial features. Recently, peptidoglycans, as bacterial cell wall components, have been shown to exist in the envelopes of moss chloroplasts. Phylogenomic comparisons of bacterial and plant genomes have raised the question of whether such structures are also part of chloroplasts in angiosperms. To address this question, we visualized canonical amino acids of peptidoglycan around chloroplasts of and via click chemistry and fluorescence microscopy. Additional detection by different peptidoglycan-binding proteins from bacteria and animals supported this observation. Further experiments with D-cycloserine and AtMurE knock-out lines, both affecting putative peptidoglycan biosynthesis, revealed a central role of this pathway in plastid genesis and division. Taken together, these results indicate that peptidoglycans are integral parts of plastids in the whole plant lineage. Elucidating their biosynthesis and further roles in the function of these organelles is yet to be achieved.
Topics: Arabidopsis; Peptidoglycan; Magnoliopsida; Chloroplasts; Cell Wall
PubMed: 36831230
DOI: 10.3390/cells12040563 -
ELife Mar 2017As infectious diseases pose a threat to host integrity, eukaryotes have evolved mechanisms to eliminate pathogens. In addition to develop strategies reducing infection,...
As infectious diseases pose a threat to host integrity, eukaryotes have evolved mechanisms to eliminate pathogens. In addition to develop strategies reducing infection, animals can engage in behaviors that lower the impact of the infection. The molecular mechanisms by which microbes impact host behavior are not well understood. We demonstrate that bacterial infection of females reduces oviposition and that peptidoglycan, the component that activates antibacterial response, is also the elicitor of this behavioral change. We show that peptidoglycan regulates egg-laying rate by activating NF-κB signaling pathway in octopaminergic neurons and that, a dedicated peptidoglycan degrading enzyme acts in these neurons to buffer this behavioral response. This study shows that a unique ligand and signaling cascade are used in immune cells to mount an immune response and in neurons to control fly behavior following infection. This may represent a case of behavioral immunity.
Topics: Animals; Drosophila; NF-kappa B; Neurons; Oviposition; Peptidoglycan; Receptors, Biogenic Amine; Signal Transduction
PubMed: 28264763
DOI: 10.7554/eLife.21937 -
Protein Science : a Publication of the... Nov 2023Bacterial WxL proteins contain peptidoglycan-binding WxL domains, which have a dual Trp-x-Leu motif and are involved in virulence. It was recently shown that WxL...
Bacterial WxL proteins contain peptidoglycan-binding WxL domains, which have a dual Trp-x-Leu motif and are involved in virulence. It was recently shown that WxL proteins occur in gene clusters, containing typically a small WxL protein (which in the mature protein consists only of a WxL domain), a large WxL protein (which contains a C-terminal WxL domain with N-terminal host-binding domains), and a conserved protein annotated as a Domain of Unknown Function (DUF). Here we analyze this DUF and show that it contains two tandem domains-DUF916 and DUF3324-which both have an IgG-like fold and together form a single functional unit, connected to a C-terminal transmembrane helix. DUF3324 is a stable domain, while DUF916 is less stable and is likely to require a stabilizing interaction with WxL. The protein is suggested to have an important role to bind and stabilize WxL on the peptidoglycan surface, via the DUF916 domain, and to bind to host cells via the DUF3324 domain. AlphaFold2 predicts that a β-hairpin strand from DUF916 inserts into WxL adjacent to its N-terminus. We therefore propose to rename the DUF916-DUF3324 pair as WxL Interacting Protein (WxLIP), with DUF916, DUF3324 and the transmembrane helix forming the first, second and third domains of WxLIP, which we characterize as peptidoglycan binding domain (PGBD), host binding domain (HBD), and transmembrane helix (TMH) respectively.
Topics: Peptidoglycan; Bacterial Proteins; Protein Binding; Virulence
PubMed: 37833244
DOI: 10.1002/pro.4806 -
European Journal of Pharmaceutical... Dec 2023Staphylococcus aureus is an important pathogenic bacterium responsible for various organ infections. The serious side effects and the development of antibiotic...
Staphylococcus aureus is an important pathogenic bacterium responsible for various organ infections. The serious side effects and the development of antibiotic resistance have rendered the antibiotic therapy against S. aureus increasingly challenging, emphasizing the pressing need for the exploration of novel therapeutic agents. Our research has uncovered the promising antimicrobial properties of 8-octyl berberine (OBBR), a novel compound derived from berberine (BBR), against S. aureus. OBBR exhibited a minimum inhibitory concentration (MIC) of 1.0 μg/mL, which closely approximated that of levofloxacin. Intriguingly, a multipassage resistance assay demonstrated that the MIC of OBBR against S. aureus remained relatively stable, while levofloxacin exhibited a 4-fold increase over 20 days, suggesting that OBBR was less prone to inducing resistance. Mechanistically, our investigation, employing Zeta potential measurements, flow cytometry, scanning electron microscopy, and transmission electron microscopy, unveiled that OBBR induced morphological alterations in the bacteria. Furthermore, it disrupted the bacterial cell wall and membrane by altering membrane potential and compromising membrane integrity. These actions culminated in bacterial disintegration and apoptosis. Transcriptomic analysis shed light on significant downregulation of gene ontology terms, predominantly associated with membranes. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis implicated OBBR in disturbing peptidoglycan biosynthesis, with the membrane protein MraY emerging as a potential target for OBBR's action against S. aureus. Notably, experiments involving the overexpression of MraY confirmed OBBR's inhibitory effect on peptidoglycan synthesis. Furthermore, molecular docking and cellular thermal shift assay revealed OBBR's direct interaction with MraY, potentially leading to the inhibition of the enzymatic activity of MraY and, consequently, impeding peptidoglycan synthesis. In summary, OBBR, by targeting MraY and inhibiting peptidoglycan synthesis, emerges as a promising alternative antibiotic against S. aureus, offering potential advantages in terms of limited drug resistance development.
Topics: Humans; Staphylococcus aureus; Berberine; Peptidoglycan; Molecular Docking Simulation; Levofloxacin; Anti-Bacterial Agents; Staphylococcal Infections; Microbial Sensitivity Tests
PubMed: 37806408
DOI: 10.1016/j.ejps.2023.106602 -
Molecular Microbiology Jul 2013The peptidoglycan (PG) cell wall is a unique macromolecule responsible for both shape determination and cellular integrity under osmotic stress in virtually all... (Review)
Review
The peptidoglycan (PG) cell wall is a unique macromolecule responsible for both shape determination and cellular integrity under osmotic stress in virtually all bacteria. A quantitative understanding of the relationships between PG architecture, morphogenesis, immune system activation and pathogenesis can provide molecular-scale insights into the function of proteins involved in cell wall synthesis and cell growth. High-performance liquid chromatography (HPLC) has played an important role in our understanding of the structural and chemical complexity of the cell wall by providing an analytical method to quantify differences in chemical composition. Here, we present a primer on the basic chemical features of wall structure that can be revealed through HPLC, along with a description of the applications of HPLC PG analyses for interpreting the effects of genetic and chemical perturbations to a variety of bacterial species in different environments. We describe the physical consequences of different PG compositions on cell shape, and review complementary experimental and computational methodologies for PG analysis. Finally, we present a partial list of future targets of development for HPLC and related techniques.
Topics: Bacteria; Cell Wall; Chromatography, High Pressure Liquid; Peptidoglycan
PubMed: 23679048
DOI: 10.1111/mmi.12266 -
Microbial Drug Resistance (Larchmont,... Jun 2014The peptidoglycan (PG) cell wall constitutes the main defense barrier of bacteria against environmental insults and acts as communication interface. The biochemistry of... (Review)
Review
The peptidoglycan (PG) cell wall constitutes the main defense barrier of bacteria against environmental insults and acts as communication interface. The biochemistry of this macromolecule has been well characterized throughout the years but recent discoveries have unveiled its chemical plasticity under environmental stresses. Non-canonical D-amino acids (NCDAA) are produced and released to the extracellular media by diverse bacteria. Such molecules govern cell wall adaptation to challenging environments through their incorporation into the polymer, a widespread capability among bacteria that reveals the inherent catalytic plasticity of the enzymes involved in the cell wall metabolism. Here, we analyze the recent structural and biochemical characterization of Bsr, a new family of broad spectrum racemases able to generate a wide range of NCDAA. We also discuss the necessity of a coordinated action of PG multispecific enzymes to generate adequate levels of modification in the murein sacculus. Finally, we also highlight how this catalytic plasticity of NCDAA-incorporating enzymes has allowed the development of new revolutionary methodologies for the study of PG modes of growth and in vivo dynamics.
Topics: Adaptation, Physiological; Amino Acid Isomerases; Amino Acids; Bacterial Proteins; Catalytic Domain; Cell Wall; Metabolic Networks and Pathways; Models, Molecular; Peptidoglycan; Stress, Physiological; Vibrio cholerae
PubMed: 24799190
DOI: 10.1089/mdr.2014.0047 -
Current Opinion in Microbiology Dec 2013A bacterial cell takes on the challenge to preserve and reproduce its shape at every generation against a substantial internal pressure by surrounding itself with a... (Review)
Review
A bacterial cell takes on the challenge to preserve and reproduce its shape at every generation against a substantial internal pressure by surrounding itself with a mechanical support, a peptidoglycan cell wall. The enlargement of the cell wall via net incorporation of precursors into the pre-existing wall conditions bacterial growth and morphology. However, generation, reproduction and/or modification of a specific shape requires that the incorporation takes place at precise locations for a defined time period. Much has been learnt in the past few years about the biochemistry of the peptidoglycan synthesis process, but topological approaches to the understanding of shape generation have been hindered by a lack of appropriate techniques. Recent technological advances are paving the way for substantial progress in understanding the mechanisms of bacterial morphogenesis. Here we review the latest developments, focusing on the impact of new techniques on the precise mapping of cell wall growth sites.
Topics: Bacteria; Cell Wall; Microbiology; Peptidoglycan
PubMed: 24094807
DOI: 10.1016/j.mib.2013.09.004 -
Microbial Biotechnology Jan 2017Clostridium difficile infection (CDI) is a challenging threat to human health. Infections occur after disruption of the normal microbiota, most commonly through the use... (Review)
Review
Clostridium difficile infection (CDI) is a challenging threat to human health. Infections occur after disruption of the normal microbiota, most commonly through the use of antibiotics. Current treatment for CDI largely relies on the broad-spectrum antibiotics vancomycin and metronidazole that further disrupt the microbiota resulting in frequent recurrence, highlighting the need for C. difficile-specific antimicrobials. The cell surface of C. difficile represents a promising target for the development of new drugs. C. difficile possesses a highly deacetylated peptidoglycan cell wall containing unique secondary cell wall polymers. Bound to the cell wall is an essential S-layer, formed of SlpA and decorated with an additional 28 related proteins. In addition to the S-layer, many other cell surface proteins have been identified, including several with roles in host colonization. This review aims to summarize our current understanding of these different C. difficile cell surface components and their viability as therapeutic targets.
Topics: Bacterial Proteins; Cell Wall; Clostridioides difficile; Membrane Glycoproteins; Peptidoglycan
PubMed: 27311697
DOI: 10.1111/1751-7915.12372 -
Microbiology (Reading, England) Feb 2006Surface-exposed proteins are key players during the infectious process of pathogenic bacteria. The cell surface of the Gram-positive human pathogen Streptococcus... (Review)
Review
Surface-exposed proteins are key players during the infectious process of pathogenic bacteria. The cell surface of the Gram-positive human pathogen Streptococcus pneumoniae is decorated not only by typical Gram-positive surface proteins, but also by a family of proteins that recognizes the phosphorylcholine of the lipoteichoic and teichoic acids, namely the choline-binding proteins, and by non-classical surface proteins that lack a leader peptide and membrane-anchor motif. A comprehensive understanding of how microbial proteins subvert host immunity or host protein functions is a prerequisite for the development of novel therapeutic strategies to combat pneumococcal infections. This article reviews recent progress in the investigation of the versatility and sophistication of the virulence functions of surface-exposed pneumococcal proteins.
Topics: Bacterial Outer Membrane Proteins; Binding Sites; Cell Wall; Genome, Bacterial; Peptidoglycan; Protein Structure, Tertiary; Streptococcus pneumoniae; Virulence
PubMed: 16436417
DOI: 10.1099/mic.0.28610-0