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Bacterial Peptidoglycan (bacterial + peptidoglycan)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Enhanced maturation and functional capacity of monocyte-derived immature dendritic cells by the synthetic immunomodulator Murabutide

IMMUNOLOGY, Issue 4 2001
Vincent Vidal
Summary Murabutide is a safe synthetic immunomodulator derived from muramyl dipeptide, the smallest bioactive unit of bacterial peptidoglycan. Although it is well known that muramyl peptides modulate the functions of monocytes/macrophages, their activity on dendritic cells is poorly documented. We thus investigated the effects of Murabutide on immunophenotype, endocytosis, T-cell stimulatory capacity, and cytokine secretion of human monocyte-derived immature dendritic cells (iDCs). We found that Murabutide triggers immunophenotypic changes as upon treatment, iDCs up-regulate the surface expression of the major histocompatibility complex type II molecule human leucocyte antigen-DR, the co-stimulatory molecules CD80, CD86 and CD40 and the differentiation marker CD83, and down-regulate the expression of the mannose receptor. These phenotypic changes are also mirrored by changes in their biological activity. Subsequent to treatment with the synthetic immunomodulator, DC have a decreased endocytic capacity but exhibit enhanced stimulatory capacity for both allogeneic and autologous T cells. In addition, Murabutide-stimulated iDCs have a greater cytostatic activity toward the tumour cell line THP-1. Furthermore, in the presence of Murabutide, DCs transiently increased the release of macrophage inhibitory protein-1,, tumour necrosis factor-, and interleukin-10, whereas the enhanced production of macrophage-colony stimulating factor was sustained over the 3-day period analysed. In addition, Murabutide triggers the phosphorylation of the three classes of mitogen-activated protein kinases in iDCs. Altogether our results demonstrate that Murabutide triggers the maturation and activation of monocyte-derived iDCs. As this immunomodulator is approved for administration in humans, it could be a useful adjunct to boost the efficacy of DC-based vaccines designed against tumours or virus-infected cells. [source]

Gliotoxin, an inhibitor of nuclear factor-kappa B, attenuates peptidoglycan-polysaccharide-induced colitis in rats

INFLAMMATORY BOWEL DISEASES, Issue 3 2002
Dr. Leo R. Fitzpatrick
Abstract Gliotoxin is a fungal metabolite that has immunosuppressive properties. First, we determined if gliotoxin could inhibit bacterial peptidoglycan,polysaccharide-stimulated tumor necrosis factor-, production, as well as nuclear factor-kappa B (NF-,B), in a rat macrophage (NR8383) cell line. Next, the apoptosis-inducing potential of gliotoxin was also evaluated in this cell line. Finally, we evaluated whether gliotoxin could reduce peptidoglycan,polysaccharide-induced colitis in rats. Gliotoxin (2 mg/kg/day) was dosed from day 14 after the initial intramural colonic injection of peptidoglycan,polysaccharide until day 21. A gross colonic injury score, myeloperoxidase activity, and cytokine levels were all evaluated on day 21. Gliotoxin dose dependently inhibited cytokine production, as well as NF-,B, and also induced apoptosis in the NR8383 cell line. On day 21, gliotoxin significantly reduced gross colonic injury (adhesions, nodules, mucosal lesions) in rats. Gliotoxin-treated rats also had partially normalized biochemical indices of colitis, such as colonic cytokine levels. The colonic level of NF-,B was also partially normalized in gliotoxin treated rats. Gliotoxin also exhibited an antiarthritis effect in peptidoglycan,polysaccharide-treated rats. In summary, gliotoxin effectively attenuated the chronic reactivation phase of peptidoglycan,polysaccharide-induced colitis. This anticolitis effect may be related to the inhibition of NF-,B in Lewis rats. [source]

Structure of the diaminopimelate epimerase DapF from Mycobacterium tuberculosis

ACTA CRYSTALLOGRAPHICA SECTION D, Issue 4 2009
Veeraraghavan Usha
The meso (or d,l) isomer of diaminopimelic acid (DAP), a precursor of l -lysine, is a key component of the pentapeptide linker in bacterial peptidoglycan. While the peptidoglycan incorporated in the highly complex cell wall of the pathogen Mycobacterium tuberculosis structurally resembles that of Escherichia coli, it is unique in that it can contain penicillin-resistant meso -DAP,meso -DAP linkages. The interconversion of l,l -DAP and meso -DAP is catalysed by the DAP epimerase DapF, a gene product that is essential in M. tuberculosis. Here, the crystal structure of the ligand-free form of M. tuberculosis DapF (MtDapF) refined to a resolution of 2.6,Å is reported. MtDapF shows small if distinct deviations in secondary structure from the two-domain ,/,-fold of the known structures of Haemophilus influenzae DapF and Bacillus anthracis DapF, which are in line with its low sequence identity (,27%) to the former. Modelling the present structure onto that of l,l -aziridino-DAP-bound H. influenzae DapF illustrates that a rigid-body movement of domain II and a rearrangement of the B4,A2 loop (residues 80,90) of domain I are likely to accompany the transition from the present inactive form to a catalytically competent enzyme. Despite a highly conserved active-site architecture, the model indicates that stabilization of the DAP backbone occurs in MtDapF through a tyrosine residue that is specific to mycobacterial DAP epimerases. [source]

Evidence for involvement of peptidoglycan in the triggering of an oxidative burst by Listeria monocytogenes in phagocytes

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2005
K. A. Remer
Summary We have shown previously that in listeric encephalitis of cattle and rats, nitrotyrosine was produced in microabscesses, implying that both superoxide anion (O2,) and nitric oxide (NO) are present and react with each other. Evidence of local synthesis of NO by macrophages was provided, but the source of O2, remained unknown. Here we have examined whether phagocytes exposed to viable and heat-killed Listeria monocytogenes (LM,) produce O2, and, if so, whether this results from direct interaction of phagocytes with the bacterial surface of L. monocytogenes or whether prior opsonization is required. Using lucigenin-enhanced chemiluminescence (LCL) for the measurement of O2,, we show that LM, induces an oxidative burst in human neutrophils, monocytes and monocyte-derived macrophages (M,). Viability is not required, and opsonization by antibodies and/or complement does not enhance the LCL signal. As Toll-like receptors (TLR) were shown recently to mediate an oxidative burst, TLR agonists representative for pathogen-associated molecular patterns (PAMPs) were tested for their ability to elicit an oxidative burst. These included lipoteichoic acid (LTA), bacterial peptidoglycan (PGN), recombinant flagellin, CpG-containing DNA and double-stranded RNA. Only PGN and flagellin consistently elicited an LCL signal resembling that induced by LM, with regard to the kinetics and cell spectrum stimulated. However, flagellin was unlikely to be responsible for the LM,-mediated burst, as a flagellin-deficient mutant showed no decrease in LCL. We therefore assume that in LM,, core PGN acts as a PAMP and directly induces an oxidative burst in all phagocyte populations. We conclude that in cerebral lesions superoxide anion is generated locally by phagocytes recognizing bacterial PGN. [source]