Abstract

Outer membrane vesicles (OMVs) produced by Gram-negative bacteria and their RNA content have recently received increasing attention as novel mediators of host-guest intercellular and interspecies communication. These kinds of vesicles allow not only the export of proteins, but also of DNA and other small RNAs. We previously reported that the production of bacterial vesicles could represent a way to communicate with the surrounding environment. This general mechanism, exploited by bacteria and viruses, allows conveying “messages” to the surrounding cells and tissues, thus leading to the manipulation of the host immune response. Many functions attributed to OMVs are a consequence of their high capability to survive in different environmental stressors and to enter into cells quite easily. As these properties can be exploited to advantage human health, in this review, we summarized the papers that reported the use of OMVs as modulators of cellular activities through the involvement of the RNAs contained within. We also discussed what has been done with OMVs and what remains to be discovered in order to prompt the investigations toward the complete elucidation of the role and functions of these vesicles.

Highlights

  • It is well acknowledged that bacteria are able to secrete extracellular vesicles (EVs) in the surrounding environment and that these vesicles are employed to communicate with other cells (Lee et al, 2009; Deatherage and Cookson, 2012; Kim et al, 2015)

  • As we believe that the regulatory potential of RNA molecules, including microRNAs, can have a significant impact on modulating critical biological processes in human cells, affecting human health, we focused the discussion on the most recent studies reported in the literature dealing with the delivery of outer membrane vesicles (OMVs) containing small RNAs (sRNAs) molecules

  • Despite numerous papers demonstrated the effects of OMVs on human cells, either mediated by proteins or nucleic acids, the exact mechanisms of bacterial vesicles and their content are still largely unknown

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Summary

INTRODUCTION

It is well acknowledged that bacteria are able to secrete extracellular vesicles (EVs) in the surrounding environment and that these vesicles are employed to communicate with other cells (Lee et al, 2009; Deatherage and Cookson, 2012; Kim et al, 2015). We will discuss our opinion on what should be discovered in the field of bacterial OMVs and prompt the investigations toward the complete elucidation of the roles and functions of these vesicles and their sRNAs. Bacterial sRNAs (i.e., tRNA fragments) can be internalized within extracellular vesicles, released in the surrounding environment, and transferred to other microbes and host cells (Koeppen et al, 2016; Tsatsaronis et al, 2018; Lee, 2019) as already reported by the protozoan pathogen Trypanosoma cruzi (Garcia-Silva et al, 2014). The Pseudomonas aeruginosa-derived methionine tRNA can be conveyed by OMVs into human epithelial airway cells and decreases the secretion of IL-8 (Koeppen et al, 2016) All of these studies emphasize the importance of microbial sRNAs as crucial communication molecules that are able to mediate host-microbe interactions

BACTERIAL sRNAs
BIOGENESIS OF OMVs
CHARACTERIZATION OF THE RNA CONTENT OF BACTERIAL OMVs
UPTAKE OF OMVs BY HUMAN CELLS
Streptococcus mutans
DELIVERY OF sRNAs BY OMVs AND THEIR EFFECT ON HUMAN CELLS
CONCLUSIONS AND PERSPECTIVES
AUTHOR CONTRIBUTIONS
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