sncRNAs packaged by Helicobacter pylori outer membrane vesicles attenuate IL-8 secretion in human cells

Zhang, Hongxia; Zhang, Yingxuan; Song, Zifan; Li, Ruizhen; Ruan, Huan; Liu, Qiong; Huang, Xiaotian

doi:10.1016/j.ijmm.2019.151356

Cited by 62 publications

(51 citation statements)

References 34 publications

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“…Second, the relative abundance of several RNAs between two environmental conditions was different in the EVs and the EV-producing cells. Other studies also found that some RNA populations were enriched in EVs from Gramnegative and Gram-positive pathogenic bacteria (Ghosal et al, 2015;Koeppen et al, 2016;Resch et al, 2016;Malabirade et al, 2018;Malge et al, 2018;Han et al, 2019;Langlete et al, 2019;Zhang et al, 2020). This notably includes sRNAs, which can play regulatory activity in the host (Koeppen et al, 2016;Malabirade et al, 2018;Langlete et al, 2019;Zhang et al, 2020).…”

Section: Discussionmentioning

confidence: 94%

Environmental Plasticity of the RNA Content of Staphylococcus aureus Extracellular Vesicles

et al. 2021

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The roles of bacterial extracellular vesicles (EVs) in cell-to-cell signaling are progressively being unraveled. These membranous spheres released by many living cells carry various macromolecules, some of which influence host-pathogen interactions. Bacterial EVs contain RNA, which may serve in communicating with their infected hosts. Staphylococcus aureus, an opportunistic human and animal pathogen, produces EVs whose RNA content is still poorly characterized. Here, we investigated in depth the RNA content of S. aureus EVs. A high-throughput RNA sequencing approach identified RNAs in EVs produced by the clinical S. aureus strain HG003 under different environmental conditions: early- and late-stationary growth phases, and presence or absence of a sublethal vancomycin concentration. On average, sequences corresponding to 78.0% of the annotated transcripts in HG003 genome were identified in HG003 EVs. However, only ~5% of them were highly covered by reads (≥90% coverage) indicating that a large fraction of EV RNAs, notably mRNAs and sRNAs, were fragmented in EVs. According to growth conditions, from 86 to 273 highly covered RNAs were identified into the EVs. They corresponded to 286 unique RNAs, including 220 mRNAs. They coded for numerous virulence-associated factors (hld encoded by the multifunctional sRNA RNAIII, agrBCD, psmβ1, sbi, spa, and isaB), ribosomal proteins, transcriptional regulators, and metabolic enzymes. Twenty-eight sRNAs were also detected, including bona fide RsaC. The presence of 22 RNAs within HG003 EVs was confirmed by reverse transcription quantitative PCR (RT-qPCR) experiments. Several of these 286 RNAs were shown to belong to the same transcriptional units in S. aureus. Both nature and abundance of the EV RNAs were dramatically affected depending on the growth phase and the presence of vancomycin, whereas much less variations were found in the pool of cellular RNAs of the parent cells. Moreover, the RNA abundance pattern differed between EVs and EV-producing cells according to the growth conditions. Altogether, our findings show that the environment shapes the RNA cargo of the S. aureus EVs. Although the composition of EVs is impacted by the physiological state of the producing cells, our findings suggest a selective packaging of RNAs into EVs, as proposed for EV protein cargo. Our study shedds light to the possible roles of potentially functional RNAs in S. aureus EVs, notably in host-pathogen interactions.

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Section: Discussionmentioning

confidence: 94%

Environmental Plasticity of the RNA Content of Staphylococcus aureus Extracellular Vesicles

et al. 2021

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“…In addition to dsDNA, several studies have shown the presence of small RNAs in H. pylori OMVs, and suggested a functional role upon their transfer into host cells [ 51 , 52 ]. More than a half million unique small non-coding (snc) RNA sequences were identified by RNA seq of OMVs purified from the supernatants of H. pylori strain J99, and RNAse protection assays for selected sncRNAs suggested an encapsulation within the OMV lumen [ 53 ]—or at least a lower susceptibility to digestion due to OMV binding and protection by a protein corona on the OMV surface, as has been suggested for small RNAs in mammalian EVs [ 54 , 55 ]. The uptake of sncRNAs into AGS cells was suggested by quantitative RT- PCR and microscopy using double labeling with a lipid dye (DiI) and an unspecific RNA intercalating dye.…”

Section: The Content Of H Pylori Omvsmentioning

confidence: 99%

“…Of note, the lipid labeling of mammalian EVs can easily give rise to a number of artefacts, including micelle formation, unspecific labeling of other particles within the heterogeneous samples and the secondary redistribution of the dye, and it is conceivable that similar issues also apply for OMVs. Nevertheless, this study reports a functional effect of the H. pylori OMV on LPS-stimulated interleukin-8 (IL-8) secretion by gastric epithelial AGS cells, and has convincingly attributed it to two candidate small RNAs identified in the OMV transcriptome, and the authors hypothesized that these small RNAs might target the human IL-8 mRNA directly [ 53 ]. While more studies are required, these data suggest that small RNAs within H. pylori OMVs might play a fundamental role in directly tuning the host immune response.…”

Section: The Content Of H Pylori Omvsmentioning

confidence: 99%

“…This is in line with infection experiments investigating IL-8 secretion, which is clearly dependent on a functional T4SS, but independent of CagA translocation [ 88 ]. The sncRNAs identified in H. pylori strain J99 OMVs reduced IL-8 cytokine secretion [ 53 ], whereas it will be an interesting question to assess whether this might be mediated through a direct targeting of the IL-8 mRNA by the sncRNAs, and potential induction of RNA silencing. The fact that IL-8 is released in response to OMVs is interesting since it was further shown that OMVs also contain peptidoglycan (PG).…”

Section: The Content Of H Pylori Omvsmentioning

confidence: 99%

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Helicobacter pylori-Derived Outer Membrane Vesicles (OMVs): Role in Bacterial Pathogenesis?

et al. 2020

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Persistent infections with the human pathogen Helicobacter pylori (H. pylori) have been closely associated with the induction and progression of a wide range of gastric disorders, including acute and chronic gastritis, ulceration in the stomach and duodenum, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. The pathogenesis of H. pylori is determined by a complicated network of manifold mechanisms of pathogen–host interactions, which involves a coordinated interplay of H. pylori pathogenicity and virulence factors with host cells. While these molecular and cellular mechanisms have been intensively investigated to date, the knowledge about outer membrane vesicles (OMVs) derived from H. pylori and their implication in bacterial pathogenesis is not well developed. In this review, we summarize the current knowledge on H. pylori-derived OMVs.

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“…Different assays were performed in vitro and in vivo, showing that this sRNA is transferred to cells via OMVs and plays a role in modulating the immune response by decreasing IL-8 secretion. Similarly, in Helicobacter pylori, sncRNAs sR-2509025, and sR-989262 can reduce the LPS-mediated induction of IL-8 protein secretion in human gastric adenocarcinoma cells (Zhang et al, 2020).…”

Section: Bacterial Membrane Vesiclesmentioning

confidence: 97%

Cross-Kingdom Extracellular Vesicles EV-RNA Communication as a Mechanism for Host–Pathogen Interaction

Rocha

Amatuzzi

Lucena

et al. 2020

Front. Cell. Infect. Microbiol.

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sncRNAs packaged by Helicobacter pylori outer membrane vesicles attenuate IL-8 secretion in human cells

Cited by 62 publications

References 34 publications

Environmental Plasticity of the RNA Content of Staphylococcus aureus Extracellular Vesicles

Environmental Plasticity of the RNA Content of Staphylococcus aureus Extracellular Vesicles

Helicobacter pylori-Derived Outer Membrane Vesicles (OMVs): Role in Bacterial Pathogenesis?

Cross-Kingdom Extracellular Vesicles EV-RNA Communication as a Mechanism for Host–Pathogen Interaction

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