Biological effects of a purified lipopolysaccharide from Bacteroides gingivalis

Nair, Bindukumar; Mayberry, W. R.; Dziak, Rosemary; Chen, P. B.; Levine, Martin; Hausmann, Ernest

doi:10.1111/j.1600-0765.1983.tb00333.x

Cited by 127 publications

(91 citation statements)

References 24 publications

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“…These factors include fimbriae, which are utilized for host cell invasion and subversion of Toll-like receptor responses (Njoroge et al, 1997;Hajishengallis et al, 2008) and cysteine proteases which destroy both host extra-cellular matrix components and host innate immune mediators (Takii et al, 2005). Notably, the lipopolysaccharide (LPS) of P. gingivalis exhibits an unusually low endotoxic potency in its ability to stimulate host innate immune defenses relative to the potencies that are associated with classic responses elicited by LPS derived from Gram-negative bacteria such as Escherichia coli (E. coli) (Mansheim et al, 1978;Nair et al, 1983). A number of independent studies have implicated this unusual bacterial LPS as potentially playing a role in the ability of P. gingivalis to either evade or subvert host innate immune responses.…”

Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4′‐Phosphatase, PGN_0524

Coats

Jain

et al. 2009

Int J Oral Sci

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). Approximately 2,700 independent Tn4400'-derived mutants of P. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose (50 µg⋅mL -1 ). A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400' transposon was integrated into the gene encoding the lipid A 4'-phosphatase, PGN_0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400', was highly sensitive to PMB killing relative to wild-type P.gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural (MALDI-TOF MS) analyses revealed that lipid A isolates from 0524-Tn4400' and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wildtype P. gingivalis lipid A spectrum. Finally, intact 0524-Tn4400' and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 (TLR4)-dependent E-selectin expression in human endothelial cells relative to intact wild-type P. gingivalis or its corresponding LPS isolate. Conclusion The combined molecular evidence provided in this report suggests that PGN_0524, a lipid A 4'-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, P. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as PMB. These data strongly implicate PGN_0524 as a critical virulence factor for the ability of P. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and TLR4 sensing.

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Section: Introductionmentioning

confidence: 99%

Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4′‐Phosphatase, PGN_0524

Coats

Jain

et al. 2009

Int J Oral Sci

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“…It is therefore thought to be one of the most important virulence factors, along with proteases, collagenase, and adhesins, that cause host tissue destruction in adult periodontal disease (3,7,39,40). P. gingivalis LPS displays the overall endotoxic activities of enterobacterial LPS, but the potency of the former is far more moderate than that of the latter (16,17,28,30). Furthermore, P. gingivalis LPS contains a significant amount of protein and stimulates the splenocytes of endotoxin-nonresponsive C3H/ HeJ mice to undergo mitosis (9,21,22).…”

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confidence: 99%

“…The lipopolysaccharide (LPS) of Porphyromonas gingivalis, an oral anaerobic gram-negative rod, exhibits bone resorption activity and induces various inflammatory cytokines in human gingival fibroblast cultures (14,19,30,38,42). It is therefore thought to be one of the most important virulence factors, along with proteases, collagenase, and adhesins, that cause host tissue destruction in adult periodontal disease (3,7,39,40).…”

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Structural study on the free lipid A isolated from lipopolysaccharide of Porphyromonas gingivalis

et al. 1995

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“…However, P. gingivalis LPS has a lower level of endotoxic potency than other types of enterobacterial LPSs (21,27), while it and its active center, lipid A, have been shown to have other properties, such as an ability to activate cells from LPS-hyporesponsive C3H/HeJ mice as well as those from LPS-responsive C3H/HeN mice (18,42).…”

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Lipopolysaccharide Preparation Extracted fromPorphyromonas gingivalisLipoprotein-Deficient Mutant Shows a Marked Decrease in Toll-Like Receptor 2-Mediated Signaling

et al. 2005

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We recently demonstrated that a new PG1828-encoded lipoprotein (PG1828LP) was able to be separated from a Porphyromonas gingivalis lipopolysaccharide (LPS) preparation, and we found that it exhibited strong cell activation, similar to that of Escherichia coli LPS, through a Toll-like receptor 2 (TLR2)-dependent pathway. In order to determine the virulence of PG1828LP toward cell activation, we generated a PG1828-deficient mutant of P. gingivalis strain 381 by allelic exchange mutagenesis using an ermF-ermAM antibiotic resistance cassette. A highly purified preparation of LPS from a PG1828-deficient mutant (⌬PG1828-LPS) showed nearly the same ladder-like patterns in silver-stained gels as a preparation of LPS from a wild-type strain (WT-LPS), as well as Limulus amoebocyte lysate activities that were similar to those of the WT-LPS preparation. However, the ability of the ⌬PG1828-LPS preparation to activate NF-B in TLR2-expressing cells was markedly attenuated. Cytokine production by human gingival fibroblasts was also decreased in response to the ⌬PG1828-LPS preparation in comparison with the WT-LPS preparation, and the activity was comparable to the stimulation of highly purified lipid A of P. gingivalis by TLR4. Further, lethal toxicity was rarely observed following intraperitoneal injection of the PG1828-deficient mutant into mice compared to that with the wild-type strain, while the ⌬PG1828-LPS preparation showed no lethal toxicity. Taken together, these results clearly indicate that PG1828LP plays an essential role in inflammatory responses and may be a major virulence factor of P. gingivalis.Porphyromonas gingivalis has been implicated as a major etiological agent in the development and progression of chronic periodontitis, which is a destructive inflammatory disease of the supporting tissues of the teeth (38). This bacterium is a gram-negative, obligate anaerobic, oral black-pigmented rod that possesses a large number of potential virulence factors, such as fimbriae, hemagglutinin, lipopolysaccharide (LPS), and various proteases (15).Among these virulence factors, LPS is well known as a major component of the outer membranes of gram-negative bacteria, and it exhibits powerful immunostimulatory and inflammatory activities (32). However, P. gingivalis LPS has a lower level of endotoxic potency than other types of enterobacterial LPSs (21, 27), while it and its active center, lipid A, have been shown to have other properties, such as an ability to activate cells from LPS-hyporesponsive C3H/HeJ mice as well as those from LPS-responsive C3H/HeN mice (18, 42).Toll-like receptor 4 (TLR4) and its accessory protein MD-2 are known to function as signaling receptors for various LPSs (44), and C3H/HeJ mice have been demonstrated to be hyporesponders, due to a natural point mutation of TLR4 (30). Further, TLR2 has been shown to be an essential signal-transducing molecule for P. gingivalis LPS preparations (4, 13), although P. gingivalis LPS is thought to be associated with quite different lipid A phosphorylation and acy...

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Biological effects of a purified lipopolysaccharide from Bacteroides gingivalis

Cited by 127 publications

References 24 publications

Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4′‐Phosphatase, PGN_0524

Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4′‐Phosphatase, PGN_0524

Structural study on the free lipid A isolated from lipopolysaccharide of Porphyromonas gingivalis

Lipopolysaccharide Preparation Extracted fromPorphyromonas gingivalisLipoprotein-Deficient Mutant Shows a Marked Decrease in Toll-Like Receptor 2-Mediated Signaling

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