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Published on: March 31, 2021
A Novel Mechanism of Host-Pathogen Interaction through sRNA in Bacterial Outer Membrane Vesicles
Katja Koeppen1, Thomas H Hampton1, Michael Jarek2
1Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Abstract:
Bacterial outer membrane vesicle (OMV)-mediated delivery of proteins to host cells is an important mechanism of host-pathogen communication. Emerging evidence suggests that OMVs contain differentially packaged short RNAs (sRNAs) with the potential to target host mRNA function and/or stability. In this study, we used RNA-Seq to characterize differentially packaged sRNAs in Pseudomonas aeruginosa OMVs, and to show transfer of OMV sRNAs to human airway cells. We selected one sRNA for further study based on its stable secondary structure and predicted mRNA targets. Our candidate sRNA (sRNA52320), a fragment of a P. aeruginosa methionine tRNA, was abundant in OMVs and reduced LPS-induced as well as OMV-induced IL-8 secretion by cultured primary human airway epithelial cells. We also showed that sRNA52320 attenuated OMV-induced KC cytokine secretion and neutrophil infiltration in mouse lung. Collectively, these findings are consistent with the hypothesis that sRNA52320 in OMVs is a novel mechanism of host-pathogen interaction whereby P. aeruginosa reduces the host immune response.
Insights
Pseudomonas aeruginosa outer membrane vesicles (OMVs) deliver short RNAs (sRNAs) to host cells. One OMV-derived sRNA (sRNA52320) suppresses host immune responses, indicating a novel host-pathogen interaction mechanism.
Area of Science:
- Microbiology
- Immunology
- Molecular Biology
Background:
- Bacterial outer membrane vesicles (OMVs) mediate host-pathogen communication.
- OMVs can package short RNAs (sRNAs) that may modulate host cell functions.
- Pseudomonas aeruginosa is a significant human pathogen.
Purpose of the Study:
- To characterize sRNAs packaged within P. aeruginosa OMVs.
- To investigate the transfer of OMV sRNAs to human airway cells.
- To determine the role of a specific OMV-derived sRNA in modulating host immune responses.
Main Methods:
- RNA-sequencing (RNA-Seq) to profile OMV sRNAs.
- Co-culture of human airway epithelial cells with P. aeruginosa OMVs.
- In vitro assays measuring cytokine secretion (IL-8, KC).
- In vivo mouse model of lung inflammation.
Main Results:
- P. aeruginosa OMVs contain differentially packaged sRNAs, including sRNA52320, a tRNA fragment.
- OMV sRNAs were successfully transferred to human airway cells.
- sRNA52320 significantly reduced IL-8 secretion induced by LPS and OMVs.
- sRNA52320 attenuated OMV-induced KC cytokine secretion and neutrophil infiltration in mouse lungs.
Conclusions:
- P. aeruginosa OMVs deliver functional sRNAs to host cells.
- sRNA52320 represents a novel mechanism by which P. aeruginosa dampens the host immune response.
- Targeting OMV-mediated sRNA delivery could offer new therapeutic strategies against P. aeruginosa infections.
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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...