The functional RNA cargo of bacterial membrane vesicles

Dauros-Singorenko, Priscila; Blenkiron, Cherie; Phillips, Anthony R.J.; Swift, Simon

doi:10.1093/femsle/fny023

Cited by 64 publications

(46 citation statements)

References 102 publications

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“…That bacterial RNA and DNA can drive host immune responses and determining whether such responses are protective or detrimental to the host has been the subject of the majority of studies on immunomodulatory nucleic acids [1][2][3]5 . In comparison, fewer studies have examined how those immunomodulatory nucleic acids are secreted by bacteria in general-and by the extracellular human pathogen S. aureus in particular-and how they are transferred to host cells to eventually reach IFN signaling receptors 2,3,[18][19][20] . In conjunction with an increasing number of studies showing secretion of bacterial RNA and DNA via extracellular vesicle production [18][19][20] , we hypothesized that S. aureus secrete MVs containing bacterially-derived RNA and DNA molecules that can withstand nuclease degradation and be delivered into host cells.…”

Section: Discussionmentioning

confidence: 99%

“…In comparison, fewer studies have examined how those immunomodulatory nucleic acids are secreted by bacteria in general-and by the extracellular human pathogen S. aureus in particular-and how they are transferred to host cells to eventually reach IFN signaling receptors 2,3,[18][19][20] . In conjunction with an increasing number of studies showing secretion of bacterial RNA and DNA via extracellular vesicle production [18][19][20] , we hypothesized that S. aureus secrete MVs containing bacterially-derived RNA and DNA molecules that can withstand nuclease degradation and be delivered into host cells. In this report we show for the first time that in cultured mouse macrophages, IFN-ß mRNA induction can be triggered by purified S. aureus MVs.…”

Section: Discussionmentioning

confidence: 99%

“…Bitto et al also recently reported that chromosomal DNA fragments can be delivered to the nucleus of cultured lung epithelial cells by P. aeruginosa OMVs 17 . While such findings have catalyzed an interest in further understanding the functional roles of microbial vesicle-associated nucleic acids and how they modulate the immune response during infection [18][19][20] , these studies have not reported on the specific mechanisms by which OMVassociated RNA and DNA are taken up by host cells or provided evidence to show that OMV-associated nucleic acids interact directly with host cells to modulate the immune response. Additionally, studies of the extracellular vesicles produced by Gram-positive bacteria (termed membrane vesicles, MVs) have primarily focused on their proteinaceous cargo, with limited characterization of the MV-associated RNA and DNA content [21][22][23][24] .…”

Section: Introductionmentioning

confidence: 99%

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Staphylococcus aureussecretes immunomodulatory RNA and DNA via membrane vesicles

Rodriguez

Kuehn

2020

Preprint

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Bacterial-derived RNA and DNA can function as ligands for intracellular receptor activation and induce downstream signaling to modulate the host response to bacterial infection. The mechanisms underlying the secretion of immunomodulatory RNA and DNA by pathogens such as Staphylococcus aureus and their delivery to intracellular host cell receptors are not well understood. Recently, extracellular membrane vesicle (MV) production has been proposed as a general secretion mechanism that could facilitate the delivery of functional bacterial nucleic acids into host cells. S. aureus produce membrane-bound, spherical, nano-sized, MVs packaged with a select array of bioactive macromolecules and they have been shown to play important roles in bacterial virulence and in immune modulation through the transmission of biologic signals to host cells. Here we show that S. aureus secretes RNA and DNA molecules that are mostly protected from degradation by their association with MVs. Importantly, we demonstrate that MVs can be delivered into cultured macrophage cells and subsequently stimulate a potent IFN-β response in recipient cells via activation of endosomal Toll-like receptors. These findings advance our understanding of the mechanisms by which bacterial nucleic acids traffic extracellularly to trigger the modulation of host immune responses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Staphylococcus aureussecretes immunomodulatory RNA and DNA via membrane vesicles

Rodriguez

Kuehn

2020

Preprint

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“…Membrane vesicles consist of various types of lipids derived from cellular membranes along with numerous other biomolecules, such as membrane, periplasmic, and cytoplasmic proteins; DNA; RNA; and low molecular mass organic compounds that confer various biological functions (Brown et al, 2015;Schwechheimer and Kuehn, 2015;Dauros-Singorenko et al, 2018;Toyofuku et al, 2019). Recent studies have shown that there are different pathways of MV biogenesis, which produce different types of MVs (Toyofuku et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Cracking Open Bacterial Membrane Vesicles

2020

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Membrane vesicles (MVs) are nanoparticles composed of lipid membranes that are produced by both Gram-negative and Gram-positive bacteria. MVs have been assigned diverse biological functions, and they show great potential for applications in various fields. However, the mechanisms underlying their functions and biogenesis are not completely understood. Accumulating evidence shows that MVs are heterogenous, and different types of MVs with different compositions are released from the same species. To understand the origin and function of these MVs, determining the biochemical properties of MVs is important. In this review, we will discuss recent progress in understanding the biochemical composition and properties of MVs.

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“…Interestingly, OMVs contain a wide range of RNAs including ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), and small non-coding RNA (sRNA) (Ghosal et al, 2015; Ho et al, 2015; Sjöström et al, 2015; Blenkiron et al, 2016; Choi et al, 2017; Soares et al, 2017; Dauros-Singorenko et al, 2018), which indicates that OMVs are important to study in the context of extracellular RNA communication.…”

Section: Introductionmentioning

confidence: 99%

The RNA Complement of Outer Membrane Vesicles From Salmonella enterica Serovar Typhimurium Under Distinct Culture Conditions

et al. 2018

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Bacterial outer membrane vesicles (OMVs), as well as OMV-associated small RNAs, have been demonstrated to play a role in host–pathogen interactions. The presence of larger RNA transcripts in OMVs has been less studied and their potential role in host–pathogen interactions remains largely unknown. Here we analyze RNA from OMVs secreted by Salmonella enterica serovar Typhimurium (S. Typhimurium) cultured under different conditions, which mimic host–pathogen interactions. S. Typhimurium was grown to exponential and stationary growth phases in minimal growth control medium (phosphate-carbon-nitrogen, PCN), as well as in acidic and phosphate-depleted PCN, comparable to the macrophage environment and inducing therefore the expression of Salmonella pathogenicity island 2 (SPI-2) genes. Moreover, Salmonella pathogenicity island 1 (SPI-1), which is required for virulence during the intestinal phase of infection, was induced by culturing S. Typhimurium to the stationary phase in Lysogeny Broth (LB). For each condition, we identified OMV-associated RNAs that are enriched in the extracellular environment relative to the intracellular space. All RNA classes could be observed, but a vast majority of rRNA was exported in all conditions in variable proportions with a notable decrease in LB SPI-1 inducing media. Several mRNAs and ncRNAs were specifically enriched in/on OMVs dependent on the growth conditions. Important to note is that some RNAs showed identical read coverage profiles intracellularly and extracellularly, whereas distinct coverage patterns were observed for other transcripts, suggesting a specific processing or degradation. Moreover, PCR experiments confirmed that distinct RNAs were present in or on OMVs as full-length transcripts (IsrB-1/2; IsrA; ffs; SsrS; CsrC; pSLT035; 10Sa; rnpB; STM0277; sseB; STM0972; STM2606), whereas others seemed to be rather present in a processed or degraded form. Finally, we show by a digestion protection assay that OMVs are able to prevent enzymatic degradation of given full-length transcripts (SsrS, CsrC, 10Sa, and rnpB). In summary, we show that OMV-associated RNA is clearly different in distinct culture conditions and that at least a fraction of the extracellular RNA is associated as a full-length transcripts with OMVs, indicating that some RNAs are protected by OMVs and thereby leaving open the possibility that those might be functionally active.

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The functional RNA cargo of bacterial membrane vesicles

Cited by 64 publications

References 102 publications

Staphylococcus aureussecretes immunomodulatory RNA and DNA via membrane vesicles

Staphylococcus aureussecretes immunomodulatory RNA and DNA via membrane vesicles

Cracking Open Bacterial Membrane Vesicles

The RNA Complement of Outer Membrane Vesicles From Salmonella enterica Serovar Typhimurium Under Distinct Culture Conditions

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