Gram-negative bacterial sRNAs encapsulated in OMVs: an emerging class of therapeutic targets in diseases

Abstract

Small regulatory RNAs (sRNAs) encapsulated in outer membrane vesicles (OMVs) are critical post-transcriptional regulators of gene expression in prokaryotic and eukaryotic organisms. OMVs are small spherical structures released by Gram-negative bacteria that serve as important vehicles for intercellular communication and can also play an important role in bacterial virulence and host-pathogen interactions. These molecules can interact with mRNAs or proteins and affect various cellular functions and physiological processes in the producing bacteria. This review aims to provide insight into the current understanding of sRNA localization to OMVs in Gram-negative bacteria and highlights the identification, characterization and functional implications of these encapsulated sRNAs. By examining the research gaps in this field, we aim to inspire further exploration and progress in investigating the potential therapeutic applications of OMV-encapsulated sRNAs in various diseases.

Keywords: diseases; extracellular vesicles; gram-negative bacteria; sRNA; therapeutics.

Figure 1

Actual and schematic structure of OMVs. Steps of OMVs biogenesis in Gram-negative bacteria. The arrows indicate OMVs. SEM, scanning electron microscope; TEM, transmission electron microscopy.

Figure 2

The mode of action of the OMV-encapsulated sRNA of P. aeruginosa in human airway epithelial cells. P. aeruginosa produces OMVs after entering the mucosal layer of the airways. (1) OMVs bind to TLRs through PAMPs. (2) The MAP-kinase (TLR/MAPK) signaling pathway is activated and induces the host’s innate immune response. (3) Transcription factors are activated and cause up-regulation of IL-8 mRNA and IL-8 secretion (4) IL-8 attracts neutrophils and they phagocytose P. aeruginosa by entering the lungs. (5) OMVs fuse with sRNA and enter cells, which by targeting mRNA of the MAPK signaling pathway upstream of IL-8 leads to reduced host IL-8 secretion and neutrophil recruitment. Solid arrows, direct inhibitor; Dashed arrows, indirect inhibitor.