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FEMS Microbiology Reviews Mar 2008The normal, unmodified glycan strands of bacterial peptidoglycan consist of alternating residues of beta-1,4-linked N-acetylmuramic acid and N-acetylglucosamine. In many... (Review)
Review
The normal, unmodified glycan strands of bacterial peptidoglycan consist of alternating residues of beta-1,4-linked N-acetylmuramic acid and N-acetylglucosamine. In many species the glycan strands become modified after their insertion into the cell wall. This review describes the structure of secondary modifications and of attachment sites of surface polymers in the glycan strands of peptidoglycan. It also provides an overview of the occurrence of these modifications in various bacterial species. Recently, enzymes responsible for the N-deacetylation, N-glycolylation and O-acetylation of the glycan strands were identified. The presence of these modifications affects the hydrolysis of peptidoglycan and its enlargement during cell growth. Glycan strands are frequently deacetylated and/or O-acetylated in pathogenic species. These alterations affect the recognition of bacteria by host factors, and contribute to the resistance of bacteria to host defence factors such as lysozyme.
Topics: Acetylation; Acetylglucosamine; Amino Acid Sequence; Bacteria; Bacterial Proteins; Lactams; Molecular Sequence Data; Muramic Acids; Peptidoglycan; Sequence Alignment
PubMed: 18070068
DOI: 10.1111/j.1574-6976.2007.00088.x -
Nature Communications May 2015Planctomycetes are intriguing microorganisms that apparently lack peptidoglycan, a structure that controls the shape and integrity of almost all bacterial cells....
Planctomycetes are intriguing microorganisms that apparently lack peptidoglycan, a structure that controls the shape and integrity of almost all bacterial cells. Therefore, the planctomycetal cell envelope is considered exceptional and their cell plan uniquely compartmentalized. Anaerobic ammonium-oxidizing (anammox) Planctomycetes play a key role in the global nitrogen cycle by releasing fixed nitrogen back to the atmosphere as N2. Here using a complementary array of state-of-the-art techniques including continuous culturing, cryo-transmission electron microscopy, peptidoglycan-specific probes and muropeptide analysis, we show that the anammox bacterium Kuenenia stuttgartiensis contains peptidoglycan. On the basis of the thickness, composition and location of peptidoglycan in K. stuttgartiensis, we propose to redefine Planctomycetes as Gram-negative bacteria. Our results demonstrate that Planctomycetes are not an exception to the universal presence of peptidoglycan in bacteria.
Topics: Ammonium Compounds; Anaerobiosis; Cell Wall; Oxidation-Reduction; Peptidoglycan; Planctomycetales
PubMed: 25962786
DOI: 10.1038/ncomms7878 -
Cellular and Molecular Life Sciences :... Jun 2007Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune... (Review)
Review
Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune system is peptidoglycan, one of the most abundant constituents of the bacterial cell wall. Insects use peptidoglycan recognition proteins to detect peptidoglycan and to activate innate immune responses. Such specialized peptidoglycan receptors appear to have evolved from phage enzymes that hydrolyze bacterial cell walls. They are able to bind specific peptidoglycan molecules with distinct chemical moieties and activate innate immune pathways by interacting with other signaling proteins. Recent X-ray crystallographic studies of the peptidoglycan recognition proteins LCa, and LCx bound to peptidoglycan have provided structural insights into recognition of peptidoglycan and activation of innate immunity in insects.
Topics: Animals; Binding Sites; Carrier Proteins; Drosophila melanogaster; Immunity, Innate; Models, Molecular; Molecular Structure; Peptidoglycan; Protein Conformation; Signal Transduction
PubMed: 17417689
DOI: 10.1007/s00018-007-6567-3 -
Frontiers in Cellular and Infection... 2019The envelope of Gram-negative bacteria is critical for survival across a wide range of environmental conditions. The inner membrane, the periplasm and the outer membrane... (Review)
Review
The envelope of Gram-negative bacteria is critical for survival across a wide range of environmental conditions. The inner membrane, the periplasm and the outer membrane form a complex compartment, home to many essential processes. Hence, constant monitoring by envelope stress response systems ensure correct biogenesis of the envelope and maintain its homeostasis. Inside the periplasm, the cell wall, made of peptidoglycan, has been under the spotlight for its critical role in bacterial growth as well as being the target of many antibiotics. While much research is centered around understanding the role of the many enzymes involved in synthesizing the cell wall, much less is known about how the cell can detect perturbations of this assembly process, and how it is regulated during stress. In this review, we explore the current knowledge of cell wall defects sensing by stress response systems, mainly in the model bacterium . We also discuss how these systems can respond to cell wall perturbations to increase fitness, and what implications this has on cell wall regulation.
Topics: Bacterial Physiological Phenomena; Cell Wall; Gene Expression Regulation, Bacterial; Gram-Negative Bacteria; Host-Pathogen Interactions; Peptidoglycan; Signal Transduction; Stress, Physiological
PubMed: 31799211
DOI: 10.3389/fcimb.2019.00380 -
Frontiers in Cellular and Infection... 2020During acute bacterial meningitis, recognition of the bacterial envelope by immune cells of the central nervous system (CNS) generates a robust response that is... (Review)
Review
During acute bacterial meningitis, recognition of the bacterial envelope by immune cells of the central nervous system (CNS) generates a robust response that is essential to clear bacteria. This response is further amplified during treatment when lytic antibiotics, required for cure, also generate a burst of highly inflammatory cell envelope debris. Different peptidoglycan (PG) subcomponents interact with neurons, glia, and the blood brain barrier resulting in the entire symptom complex of meningitis. Recently, this CNS-cell envelope signaling axis has been extended to non-inflammatory recognition of cell wall components circulating from endogenous bacteria to the brain resulting in both benefit and chronic damage. This review will describe the molecular details of a broad array of cell envelope-induced responses in the CNS and what current strategies can be implemented to improve clinical outcome.
Topics: Bacteria; Blood-Brain Barrier; Cell Membrane; Cell Wall; Peptidoglycan
PubMed: 33194834
DOI: 10.3389/fcimb.2020.588378 -
Molecular Microbiology Mar 2017Peptidoglycan (PG), an essential stress-bearing component of the bacterial cell wall, is synthesised by penicillin binding proteins (PBPs). PG synthesis at the cell...
Peptidoglycan (PG), an essential stress-bearing component of the bacterial cell wall, is synthesised by penicillin binding proteins (PBPs). PG synthesis at the cell division septum is necessary for constructing new poles of progeny cells, and cells cannot elongate without inserting new PG in the side-wall. The cell division regulator GpsB appears to co-ordinate PG synthesis at the septum during division and at the side-wall during elongation in rod-shaped and ovococcoid Gram-positive bacteria. How the control over PG synthesis is exerted is unknown. In this issue of Molecular Microbiology, Rued et al. show that in pneumococci GpsB forms complexes with PBP2a and PBP2b, and that deletion or depletion of GpsB prevents closure of the septal ring that in itself is PBP2x-dependent. Loss of GpsB can be suppressed by spontaneous mutations, including within the gene encoding the only PP2C Ser/Thr phosphatase in Streptococcus pneumoniae, indicating that GpsB plays a key - but unknown - role in protein phosphorylation in pneumococci. Rued et al. combine phenotypic and genotypic analyses of mutant strains that suggest discrepancies in the literature concerning GpsB might have arisen from accumulation of unidentified suppressors, highlighting the importance and power of strain validation and whole genome sequencing in this context.
Topics: Cell Division; Cell Wall; Penicillin-Binding Proteins; Peptidoglycan; Streptococcus pneumoniae
PubMed: 28010044
DOI: 10.1111/mmi.13612 -
Discovery Medicine Sep 2010There is considerable circumstantial evidence linking tissue pleomorphic forms of unknown origin with idiopathic chronic inflammatory, collagen, lymphoproliferative,... (Review)
Review
There is considerable circumstantial evidence linking tissue pleomorphic forms of unknown origin with idiopathic chronic inflammatory, collagen, lymphoproliferative, nephro-urological (including interstitial cystitis and prostatodynia), and neoplastic diseases. Although these forms have been observed in stained tissue histopathologic specimens for many decades, most are ignored and generally regarded as diagnostically insignificant staining artifacts or debris. It is hypothesized that these pleomorphic forms are not staining artifacts/cellular debris, but instead represent various stages in the life cycle of stressed bacteria: cell wall-deficient/defective (often called L-forms) that are difficult-to-culture or nonculturable. Essential to the thesis is that small, electron dense, non-vesiculated L-forms are the central (core) element in bacterial persistence. Depending on the stimulus received, these dense forms might be considered as undifferentiated cells, with the capacity to develop along several different routes. Hence, these altered forms created in vivo take up intracellular and/or extracellular residence; possibly establishing a sort of immune protected parasitic relationship, resisting/surviving phagocytic action, and creating subtle pathologic changes in the host during a prolonged period of tissue persistence. This might translate into an etiology for chronic inflammatory diseases, when the stressed bacteria increase in numbers and overwhelm the normal biological functions of the host. In the last few decades, an increasing percentage of the population has become immunosuppressed. Some mechanisms for this increase are aging; autoimmunity; congenital, metabolic and degenerative disorders; and AIDS. The life of a patient so affected is prolonged by therapy with hormones, antimicrobials, and immunosuppressants. It is therefore not surprising that pleomorphic, dormant, and mutant bacterial populations arise in vivo when bacteria are exposed to agents that interfere with structural components and metabolic processes necessary to survival of the microbe. Recent provocative, microbiological data lend credence to the hypothesis and corroborate the multiplicity of pleomorphic forms that develop during reproduction of L forms in vitro. It is proposed that in vivo persistence of these bacterial elements escape immune surveillance partially, completely, or may integrate with host cell organelles to create bacteria-host-cell-antigen complexes which could provoke immunopathologic consequences. Highly relevant, newly published data on modifications of gene expression, modes of division for stressed bacteria, and the paradoxical finding of peptidoglycan in L-forms are pertinent to the hypothesis that atypical, pleomorphic bacteria are the organisms operative in persistence and expression of pathology over a wide spectrum of diagnostically troublesome human diseases.
Topics: Animals; Bacteria; Cell Wall; Humans; Peptidoglycan
PubMed: 20875345
DOI: No ID Found -
EMBO Molecular Medicine Mar 2015Pattern recognition receptors link metabolite and bacteria-derived inflammation to insulin resistance during obesity. We demonstrate that NOD2 detection of bacterial...
Pattern recognition receptors link metabolite and bacteria-derived inflammation to insulin resistance during obesity. We demonstrate that NOD2 detection of bacterial cell wall peptidoglycan (PGN) regulates metabolic inflammation and insulin sensitivity. An obesity-promoting high-fat diet (HFD) increased NOD2 in hepatocytes and adipocytes, and NOD2(-/-) mice have increased adipose tissue and liver inflammation and exacerbated insulin resistance during a HFD. This effect is independent of altered adiposity or NOD2 in hematopoietic-derived immune cells. Instead, increased metabolic inflammation and insulin resistance in NOD2(-/-) mice is associated with increased commensal bacterial translocation from the gut into adipose tissue and liver. An intact PGN-NOD2 sensing system regulated gut mucosal bacterial colonization and a metabolic tissue dysbiosis that is a potential trigger for increased metabolic inflammation and insulin resistance. Gut dysbiosis in HFD-fed NOD2(-/-) mice is an independent and transmissible factor that contributes to metabolic inflammation and insulin resistance when transferred to WT, germ-free mice. These findings warrant scrutiny of bacterial component detection, dysbiosis, and protective immune responses in the links between inflammatory gut and metabolic diseases, including diabetes.
Topics: Animals; Bacteria; Cell Wall; Diet; Dysbiosis; Inflammation; Insulin Resistance; Mice; Mice, Knockout; Nod2 Signaling Adaptor Protein; Peptidoglycan
PubMed: 25666722
DOI: 10.15252/emmm.201404169 -
MBio Apr 2023Moraxella catarrhalis is found almost exclusively within the human respiratory tract. This pathobiont is associated with ear infections and the development of...
Moraxella catarrhalis is found almost exclusively within the human respiratory tract. This pathobiont is associated with ear infections and the development of respiratory illnesses, including allergies and asthma. Given the limited ecological distribution of M. catarrhalis, we hypothesized that we could leverage the nasal microbiomes of healthy children without M. catarrhalis to identify bacteria that may represent potential sources of therapeutics. was more abundant in the noses of healthy children compared to children with cold symptoms and M. catarrhalis. We cultured from nasal samples and determined that most isolates of Rothia dentocariosa and "Rothia similmucilaginosa" were able to fully inhibit the growth of M. catarrhalis , whereas isolates of Rothia aeria varied in their ability to inhibit M. catarrhalis. Using comparative genomics and proteomics, we identified a putative peptidoglycan hydrolase called ecreted ntien (SagA). This protein was present at higher relative abundance in the secreted proteomes of and than in those from non-inhibitory , suggesting that it may be involved in M. catarrhalis inhibition. We produced SagA from in Escherichia coli and confirmed its ability to degrade M. catarrhalis peptidoglycan and inhibit its growth. We then demonstrated that and reduced M. catarrhalis levels in an air-liquid interface culture model of the respiratory epithelium. Together, our results suggest that restricts M. catarrhalis colonization of the human respiratory tract . Moraxella catarrhalis is a pathobiont of the respiratory tract, responsible for ear infections in children and wheezing illnesses in children and adults with chronic respiratory diseases. Detection of M. catarrhalis during wheezing episodes in early life is associated with the development of persistent asthma. There are currently no effective vaccines for M. catarrhalis, and most clinical isolates are resistant to the commonly prescribed antibiotics amoxicillin and penicillin. Given the limited niche of M. catarrhalis, we hypothesized that other nasal bacteria have evolved mechanisms to compete against M. catarrhalis. We found that are associated with the nasal microbiomes of healthy children without Next, we demonstrated that inhibit M. catarrhalis and on airway cells. We identified an enzyme produced by called SagA that degrades M. catarrhalis peptidoglycan and inhibits its growth. We suggest that or SagA could be developed as highly specific therapeutics against M. catarrhalis.
Topics: Child; Adult; Humans; Moraxella catarrhalis; Peptidoglycan; Respiratory Sounds; Asthma
PubMed: 37010413
DOI: 10.1128/mbio.00464-23 -
Scientific Reports Jun 2022Peptidoglycan (PG) is the exoskeleton of bacterial cells and is required for their viability, growth, and cell division. Unlike most bacteria, mycobacteria possess an...
Peptidoglycan (PG) is the exoskeleton of bacterial cells and is required for their viability, growth, and cell division. Unlike most bacteria, mycobacteria possess an atypical PG characterized by a high degree of unique linkages and chemical modifications which most likely serve as important determinants of virulence and pathogenesis in mycobacterial diseases. Despite this important role, the chemical composition and molecular architecture of mycobacterial PG have yet to be fully determined. Here we determined the chemical composition of PG from Mycobacterium smegmatis using high-resolution liquid chromatography-mass spectrometry. Purified cell walls from the stationary phase were digested with mutanolysin and compositional analysis was performed on 130 muropeptide ions that were identified using an in silico PG library. The relative abundance for each muropeptide ion was measured by integrating the extracted-ion chromatogram. The percentage of crosslink per PG subunit was measured at 45%. While both 3→3 and 4→3 transpeptide cross-linkages were found in PG dimers, a high abundance of 3→3 linkages was found associated with the trimers. Approximately 43% of disaccharides in the PG of M. smegmatis showed modifications by acetylation or deacetylation. A significant number of PG trimers are found with a loss of 41.00 amu that is consistent with N-deacetylation, whereas the dimers show a gain of 42.01 amu corresponding to O-acetylation of the PG disaccharides. This suggests a possible role of PG acetylation in the regulation of cell wall homeostasis in M. smegmatis. Collectively, these data report important novel insights into the ultrastructure of mycobacterial PG.
Topics: Bacterial Proteins; Cell Wall; Chromatography, Liquid; Disaccharides; Mycobacterium smegmatis; Peptidoglycan; Tandem Mass Spectrometry
PubMed: 35773428
DOI: 10.1038/s41598-022-15324-1