An RNA-Binding Protein Secreted by a Bacterial Pathogen Modulates RIG-I Signaling

Pagliuso, Alessandro; Tham, Tristan; Allemand, Eric; Robertin, Stevens; Dupuy, Bruno; Bertrand, Quentin; Bécavin, Christophe; Koutero, Mikael; Najburg, Valérie; Nahori, Marie–Anne; Tangy, Frédéric; Stavru, Fabrizia; Bessonov, Sergey; Dessen, Andréa; Muchardt, Christian; Lebreton, Alice; Komarova, Anastassia V.; Cossart, Pascale

doi:10.1016/j.chom.2019.10.004

Cited by 47 publications

(51 citation statements)

References 55 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, two r-proteins, S1 and S4, were more abundant or specific on SD-biofilms at 24-h time point compared to ED-biofilm cells or planktonic cells at comparable time points. An RNA-binding protein was recently reported as a classically secreted protein in Listeria monocytogenes affecting virulence, which binds a subset of RNAs, leading to their accumulation in the extracellular milieu and the non-self-RNA innate immunity sensor, potentiating interferon-β production [74]. We also identified other moonlighters, such as DnaK-, ClpB-, ClpC-, and ClpP, with known protein-folding/refolding activity; inactivation of the corresponding genes has been shown to decrease the persister fraction in S. aureus [75,76].…”

Section: Stress Moonlighters and Tolerancementioning

confidence: 99%

Growth Mode and Physiological State of Cells Prior to Biofilm Formation Affect Immune Evasion and Persistence of Staphylococcus aureus

et al. 2020

View full text Add to dashboard Cite

The present study investigated Staphylococcus aureus ATCC25923 surfaceomes (cell surface proteins) during prolonged growth by subjecting planktonic and biofilm cultures (initiated from exponential or stationary cells) to label-free quantitative surfaceomics and phenotypic confirmations. The abundance of adhesion, autolytic, hemolytic, and lipolytic proteins decreased over time in both growth modes, while an opposite trend was detected for many tricarboxylic acid (TCA) cycle, reactive oxygen species (ROS) scavenging, Fe-S repair, and peptidolytic moonlighters. In planktonic cells, these changes were accompanied by decreasing and increasing adherence to hydrophobic surface and fibronectin, respectively. Specific RNA/DNA binding (cold-shock protein CspD and ribosomal proteins) and the immune evasion (SpA, ClfA, and IsaB) proteins were notably more abundant on fully mature biofilms initiated with stationary-phase cells (SDBF) compared to biofilms derived from exponential cells (EDBF) or equivalent planktonic cells. The fully matured SDBF cells demonstrated higher viability in THP-1 monocyte/macrophage cells compared to the EDBF cells. Peptidoglycan strengthening, specific urea-cycle, and detoxification enzymes were more abundant on planktonic than biofilm cells, indicating the activation of growth-mode specific pathways during prolonged cultivation. Thus, we show that S. aureus shapes its surfaceome in a growth mode-dependent manner to reach high levofloxacin tolerance (>200-times the minimum biofilm inhibitory concentration). This study also demonstrates that the phenotypic state of the cells prior to biofilm formation affects the immune-evasion and persistence-related traits of S. aureus.

show abstract

Section: Stress Moonlighters and Tolerancementioning

confidence: 99%

Growth Mode and Physiological State of Cells Prior to Biofilm Formation Affect Immune Evasion and Persistence of Staphylococcus aureus

et al. 2020

View full text Add to dashboard Cite

show abstract

“…MVs were isolated by adapting a previously described protocol 39 . Briefly, 6 liters of S. aureus Newman were grown in four 3-liter flasks to mid-exponential phase (OD600 of 1.0) and the culture was centrifuged (10,000 x g, 20 min, 4˚C).…”

Section: Membrane Vesicle Isolationmentioning

confidence: 99%

Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles

Rodriguez

Kuehn

2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

“…While previous RNA-binding domain based searches failed to predict RBPs among Salmonella's secreted virulence factors (Sharan et al 2017;Tawk et al 2017), we note that the virulence-associated protein YopD of the related pathogen Yersinia pestis is well-known to moonlight as an RBP (Chen and Anderson 2011). In addition, Listeria monocytogenes has just been shown to secret an RBP to manipulate infected host cells (Gerovac and Vogel 2019;Pagliuso et al 2019). Interrogating RNase sensitivity of Salmonella virulence-associated proteins (Supplemental Fig.…”

Section: Discussionmentioning

confidence: 88%

Global discovery of bacterial RNA-binding proteins by RNase-sensitive gradient profiles reports a new FinO domain protein

Gerovac

Mouali

Kuper

et al. 2020

RNA

View full text Add to dashboard Cite

RNA-binding proteins (RBPs) play important roles in bacterial gene expression and physiology but their true number and functional scope remain little understood even in model microbes. To advance global RBP discovery in bacteria, we here establish glycerol gradient sedimentation with RNase treatment and mass spectrometry (GradR). Applied to Salmonella enterica, GradR confirms many known RBPs such as CsrA, Hfq, and ProQ by their RNase-sensitive sedimentation profiles, and discovers the FopA protein as a new member of the emerging family of FinO/ProQ-like RBPs. FopA, encoded on resistance plasmid pCol1B9, primarily targets a small RNA associated with plasmid replication. The target suite of FopA dramatically differs from the related global RBP ProQ, revealing context-dependent selective RNA recognition by FinOdomain RBPs. Numerous other unexpected RNase-induced changes in gradient profiles suggest that cellular RNA helps to organize macromolecular complexes in bacteria. By enabling poly(A)-independent generic RBP discovery, GradR provides an important element in the quest to build a comprehensive catalog of microbial RBPs.

show abstract

An RNA-Binding Protein Secreted by a Bacterial Pathogen Modulates RIG-I Signaling

Cited by 47 publications

References 55 publications

Growth Mode and Physiological State of Cells Prior to Biofilm Formation Affect Immune Evasion and Persistence of Staphylococcus aureus

Growth Mode and Physiological State of Cells Prior to Biofilm Formation Affect Immune Evasion and Persistence of Staphylococcus aureus

Staphylococcus aureus secretes immunomodulatory RNA and DNA via membrane vesicles

Global discovery of bacterial RNA-binding proteins by RNase-sensitive gradient profiles reports a new FinO domain protein

Contact Info

Product

Resources

About