Porphyromonas gingivalis Outer Membrane Vesicles Promote Apoptosis via msRNA-Regulated DNA Methylation in Periodontitis

Fan, Ruixin; Zhou, Yi; Xu, Can; Zhong, Xianmei; He, Fanzhen; Peng, Wenzao; Li, Lü; Wang, Xiaoqian; Xu, Yan

doi:10.1128/spectrum.03288-22

Cited by 12 publications

(10 citation statements)

References 61 publications

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“… 35 The purified MVs from S. aurues USA300 were 55.23 ± 8.17 nm in diameter, consistent with previous studies. 23 , 36 We confirmed that 5 μg of USA300-derived MVs is safe for C57BL/6 mice. However, the survival rates of the MV-challenged mice decreased with increasing MV dose, and 20 μg of USA300 MVs killed all tested mice within 24 h post-injection ( Figure 1D ).…”

Section: Discussionsupporting

confidence: 67%

“… 14 S. aureus MVs can package an array of prototypic pore-forming toxins, including alpha-hemolysin, delta-hemolysin, and leukocidins. 28 , 36 However, the selective cytotoxicity of S. aureus MVs against tumor cells is unclear. One possible explanation is that the expression levels of toxin receptors vary between tumorous and non-carcinomatous cells; however, this explanation requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

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Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway

Li,

Wang,

Liu

et al. 2024

IJN

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Introduction Nanosized outer membrane vesicles (OMVs) from Gram-negative bacteria have attracted increasing interest because of their antitumor activity. However, the antitumor effects of MVs isolated from Gram-positive bacteria have rarely been investigated. Methods MVs of Staphylococcus aureu s USA300 were prepared and their antitumor efficacy was evaluated using tumor-bearing mouse models. A gene knock-in assay was performed to generate luciferase Antares2–MVs for bioluminescent detection. Cell counting kit-8 and lactic dehydrogenase release assays were used to detect the toxicity of the MVs against tumor cells in vitro. Active caspase-1 and gasdermin D (GSDMD) levels were determined using Western blot, and the tumor inhibition ability of MVs was determined in B16F10 cells treated with a caspase-1 inhibitor. Results The vesicular particles of S. aureus USA300 MVs were 55.23 ± 8.17 nm in diameter, and 5 μg of MVs remarkably inhibited the growth of B16F10 melanoma in C57BL/6 mice and CT26 colon adenocarcinoma in BALB/c mice. The bioluminescent signals correlated well with the concentrations of the engineered Antares2–MVs (R 2 = 0.999), and the sensitivity for bioluminescence imaging was 4 × 10 −3 μg. Antares2–MVs can directly target tumor tissues in vivo, and 20 μg/mL Antares2–MVs considerably reduced the growth of B16F10 and CT26 tumor cells, but not non-carcinomatous bEnd.3 cells. MV treatment substantially increased the level of active caspase-1, which processes GSDMD to trigger pyroptosis in tumor cells. Blocking caspase-1 activation with VX-765 significantly protected tumor cells from MV killing in vitro and in vivo. Conclusion S. aureus MVs can kill tumor cells by activating the pyroptosis pathway, and the induction of pyroptosis in tumor cells is a promising strategy for cancer treatment.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway

Li,

Wang,

Liu

et al. 2024

IJN

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“…Growing lines of studies have demonstrated that bacterial EVs are one of the vital underlying mechanisms behind the pathogenesis of various diseases (Xie et al 2023). It has proven that outer membrane vesicles derived from periodontal pathogens such as Porphyromonas gingivalis (Fan et al 2023) and Fusobacterium nucleatum (Chen et al 2022) could promote the progression of experimental periodontitis in mice. However, whether and how E. faecalis , as a resistant bacterium in persistent endodontic infection, could contribute to apical periodontitis pathogenesis through EVs has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis

Ma,

Deng,

et al. 2024

J Dent Res

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Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.

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“…Further, small RNAs could be delivered to the host cellular immune system via OMVs of P. gingivalis , A. actinomycetemcomitans , and T. forsythia [ 146 ]. For example, Pg -EVs can target chromobox 5 (CBX5) of PDLCs through sRNA45033 in OMVs, and promote apoptosis by regulating the methylation of p53 [ 147 ]. OMVs of periodontal pathogenic bacteria can also interact with host immune cells.…”

Section: Bevs and Periodontal Regenerationmentioning

confidence: 99%

The Applications and Potentials of Extracellular Vesicles from Different Cell Sources in Periodontal Regeneration

Huang

Wang

et al. 2023

IJMS

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Periodontitis is a chronic infectious disease worldwide that can cause damage to periodontal supporting tissues including gingiva, bone, cementum and periodontal ligament (PDL). The principle for the treatment of periodontitis is to control the inflammatory process. Achieving structural and functional regeneration of periodontal tissues is also essential and remains a major challenge. Though many technologies, products, and ingredients were applied in periodontal regeneration, most of the strategies have limited outcomes. Extracellular vesicles (EVs) are membranous particles with a lipid structure secreted by cells, containing a large number of biomolecules for the communication between cells. Numerous studies have demonstrated the beneficial effects of stem cell-derived EVs (SCEVs) and immune cell-derived EVs (ICEVs) on periodontal regeneration, which may be an alternative strategy for cell-based periodontal regeneration. The production of EVs is highly conserved among humans, bacteria and plants. In addition to eukaryocyte-derived EVs (CEVs), a growing body of literature suggests that bacterial/plant-derived EVs (BEVs/PEVs) also play an important role in periodontal homeostasis and regeneration. The purpose of this review is to introduce and summarize the potential therapeutic values of BEVs, CEVs and PEVs in periodontal regeneration, and discuss the current challenges and prospects for EV-based periodontal regeneration.

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Porphyromonas gingivalis Outer Membrane Vesicles Promote Apoptosis via msRNA-Regulated DNA Methylation in Periodontitis

Cited by 12 publications

References 61 publications

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway

Staphylococcus Aureus Membrane Vesicles Kill Tumor Cells Through a Caspase-1-Dependent Pyroptosis Pathway

Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis

The Applications and Potentials of Extracellular Vesicles from Different Cell Sources in Periodontal Regeneration

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