A Novel Mechanism of Host-Pathogen Interaction through sRNA in Bacterial Outer Membrane Vesicles

TLDR

Bacterial outer membrane vesicles (OMVs) deliver proteins to host cells, and recent evidence shows they also carry short RNAs (sRNAs) that can target host mRNA function or stability. This study aimed to profile differentially packaged sRNAs in *Pseudomonas aeruginosa* OMVs using RNA‑Seq and to demonstrate their transfer to human airway cells. The authors selected a candidate sRNA based on its stable secondary structure and predicted mRNA targets for further functional analysis. The candidate sRNA (sRNA52320), a methionine tRNA fragment abundant in OMVs, reduced IL‑8 and KC cytokine secretion in human airway epithelial cells and neutrophil infiltration in mouse lungs, supporting its role as a novel OMV‑mediated mechanism that dampens host immune responses.

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.