Bacterial extracellular vesicles: an emerging avenue to tackle diseases

Xie, Junhua; Haesebrouck, Freddy; Hoecke, Lien Van; Vandenbroucke, Roosmarijn E.

doi:10.1016/j.tim.2023.05.010

Cited by 39 publications

(13 citation statements)

References 110 publications

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“…This mechanism may be concomitant with others that increase turgor pressure and promote OM curvature. For example, OMV production could be induced by a negatively charged molecule that induces repulsion of the OM anionic charge (46,55,56) and/or the physical force induced by accumulation of misfolded or overexpressed envelope proteins (46,53).…”

Section: Resultsmentioning

confidence: 99%

“…A few routes for OMV entry into host cells have been proposed: (1) endocytosis, in eukaryotic cells it can be clathrin- or caveolin-dependent, (2) pinocytosis, an actin-induced process where nonspecific uptake of extracellular components occur, (3) by lipid rafts in the host plasma membrane via caveolins or GTPases, (4) phagocytosis, and (5) by direct membrane fusion (18,22,51,53,54,56,59,62–65,70,33,71–73,37–40,43,46,50). In that sense, OMVs have an intrinsic ability to fuse with the cell and spill their contents into the host’s cytoplasm (39,46,64,72,74).…”

Section: Resultsmentioning

confidence: 99%

“…The content of OMVs of pathogenic bacteria is involved in host cell invasion, nutrient acquisition, antibiotic resistance, immune modulation, virulence, biofilm formation and intracellular communication (35,36,51,53–56,70,71). In addition to transferring toxins to host cells, OMVs contribute to pathogen survival and maintenance of pathogenesis by evading host immunity, aiding adaptation to the stressful environment, and nutrient capture (70).…”

Section: Resultsmentioning

confidence: 99%

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Outer membrane vesicles from commensal and pathogenic anaerobic bacteria: a systematic review of literature reviews

Castro-Vargas,

Barloy-Hubler,

Acuña-Amador

2023

Preprint

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Outer membrane vesicles (OMVs) are constitutively produced by Gram-negative bacteria (GNB), those from pathogenic bacteria play key roles in pathogen-host interactions, modulating host’s immune response and promoting virulence. OMVs of commensal bacteria are fundamental in the maturation of the host immune system and to maintain intestinal homeostasis.The objective of this systematic review was to synthesize the knowledge available on literature reviews on OMVs from anaerobic GNB. The information was classified into categories: induction and biogenesis, OMVs liberation, internalization by host cells, and their interaction. The most studied OMVs are fromPorphyromonas gingivalisandBacteroidesspp.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Outer membrane vesicles from commensal and pathogenic anaerobic bacteria: a systematic review of literature reviews

Castro-Vargas,

Barloy-Hubler,

Acuña-Amador

2023

Preprint

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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.…”

Section: Discussionmentioning

confidence: 99%

“…This study showed for the first time that E. faecalis EVs can be internalized by macrophages. However, it has been found that the entry of bacterial EVs into cells relies on micropinocytosis; phagocytosis; endocytosis mediated by receptor, lipid raft, clathrin, or caveolin; or membrane fusion (Xie et al 2023). Further investigation is needed to provide more information about the pathway for E. faecalis EV internalization by macrophages.…”

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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Addressing Heterogeneity in Direct Analysis of Extracellular Vesicles and Their Analogs by Membrane Sensing Peptides as Pan‐Vesicular Affinity Probes

Gori,

Frigerio,

Gagni

et al. 2024

Advanced Science

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Extracellular vesicles (EVs), crucial mediators of cell‐to‐cell communication, hold significant diagnostic potential due to their ability to concentrate protein biomarkers in bodily fluids. However, challenges in isolating EVs from biological specimens hinder their widespread use. The preferred strategy involves direct analysis, integrating isolation and analysis solutions, with immunoaffinity methods currently dominating. Yet, the heterogeneous nature of EVs poses challenges, as proposed markers may not be as universally present as thought, raising concerns about biomarker screening reliability. This issue extends to EV‐mimics, where conventional methods may lack applicability. Addressing these challenges, the study reports on Membrane Sensing Peptides (MSP) as pan‐vesicular affinity ligands for both EVs and their non‐canonical analogs, streamlining capture and phenotyping through Single Molecule Array (SiMoA). MSP ligands enable direct analysis of circulating EVs, eliminating the need for prior isolation. Demonstrating clinical translation, MSP technology detects an EV‐associated epitope signature in serum and plasma, distinguishing myocardial infarction from stable angina. Additionally, MSP allow analysis of tetraspanin‐lacking Red Blood Cell‐derived EVs, overcoming limitations associated with antibody‐based methods. Overall, the work underlines the value of MSP as complementary tools to antibodies, advancing EV analysis for clinical diagnostics and beyond, and marking the first‐ever peptide‐based application in SiMoA technology.

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Bacterial extracellular vesicles: an emerging avenue to tackle diseases

Cited by 39 publications

References 110 publications

Outer membrane vesicles from commensal and pathogenic anaerobic bacteria: a systematic review of literature reviews

Outer membrane vesicles from commensal and pathogenic anaerobic bacteria: a systematic review of literature reviews

Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis

Addressing Heterogeneity in Direct Analysis of Extracellular Vesicles and Their Analogs by Membrane Sensing Peptides as Pan‐Vesicular Affinity Probes

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