Secretable Small RNAs via Outer Membrane Vesicles in Periodontal Pathogens

Abstract

MicroRNAs (miRNAs) have been shown to be major regulators of eukaryotic gene expression. However, bacterial RNAs comparable in size to eukaryotic miRNAs (18-22 nucleotides) have received little attention. Recently, a novel class of small RNAs similar in size to miRNAs (miRNA-size, small RNAs or msRNAs) have also been found in several bacteria. Like miRNAs, msRNAs are approximately 15 to 25 nucleotides in length, and their precursors are predicted to form a hairpin loop secondary structure. Here, we identified msRNAs in the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Treponema denticola. We examined these msRNAs using a deep sequencing method and characterized dozens of msRNAs through bioinformatic analysis. Highly expressed msRNAs were selected for further validation. The findings suggest that this class of small RNAs is well conserved across the domains of life. Indeed, msRNAs secreted via bacterial outer membrane vesicles (OMVs) were detected. The ability of bacterial OMVs to deliver RNAs into eukaryotic cells was also observed. These msRNAs in OMVs allowed us to identify their potential human immune-related target genes. Furthermore, we found that exogenous msRNAs could suppress expression of certain cytokines in Jurkat T cells. We propose msRNAs may function as novel bacterial signaling molecules that mediate bacteria-to-human interactions. Furthermore, this study may provide fresh insight into bacterial pathogenic mechanisms of periodontal diseases.

Tiny RNAs and their voyage via extracellular vesicles: Secretion of bacterial small RNA and eukaryotic microRNA

“…91,92 Recently, we and other colleagues found that msRNAs in OMVs of pathogenic bacteria can be delivered into host cells and thereby modulate host immune responses. 93,94 msRNA in P. aeruginosa reduced interleukin-8 (IL-8)…”

The RNA Complement of Outer Membrane Vesicles From Salmonella enterica Serovar Typhimurium Under Distinct Culture Conditions

“…Interestingly, OMVs contain a wide range of RNAs including ribosomal RNA (rRNA), transfer RNA (tRNA), messenger RNA (mRNA), and small non-coding RNA (sRNA) (Ghosal et al, 2015; Ho et al, 2015; Sjöström et al, 2015; Blenkiron et al, 2016; Choi et al, 2017; Soares et al, 2017; Dauros-Singorenko et al, 2018), which indicates that OMVs are important to study in the context of extracellular RNA communication.…”

Small and Smaller—sRNAs and MicroRNAs in the Regulation of Toxin Gene Expression in Prokaryotic Cells: A Mini-Review

“…This 23-nt small RNA molecule, named MM-H, is derived from a precursor stem-loop structure, requires the mammalian host cell RNA processing machinery for its biogenesis, and probably also affects the expression of the eukaryotic host, rather than bacterial genes [21]. Small RNAs comparable in size to eukaryotic microRNAs have also been identified in periodontal pathogens such as: leukotoxin LtxA—producing Aggregatibacter actinomycetemcomitans ; engaged in the production of the haemolytic toxin Porphyromonas gingivalis strain; responsible for production of highly toxic metabolites Treponema denticola bacteria [22] and a key player in the colonization of the human oral cavity Streptococcus sanguinis [49]. It was observed that the identified microRNA-size RNAs are secreted from the periodontal pathogens via bacterial outer membrane vesicles (OMVs) and affect the eukaryotic host immune system by suppressing the expression of certain cytokines [22].…”

“…Small RNAs comparable in size to eukaryotic microRNAs have also been identified in periodontal pathogens such as: leukotoxin LtxA—producing Aggregatibacter actinomycetemcomitans ; engaged in the production of the haemolytic toxin Porphyromonas gingivalis strain; responsible for production of highly toxic metabolites Treponema denticola bacteria [22] and a key player in the colonization of the human oral cavity Streptococcus sanguinis [49]. It was observed that the identified microRNA-size RNAs are secreted from the periodontal pathogens via bacterial outer membrane vesicles (OMVs) and affect the eukaryotic host immune system by suppressing the expression of certain cytokines [22]. Interestingly, OMVs serve as secretory vehicles by which pathogens not only modulate the host immune response, but also deliver toxins into host cells and are, thus, considered as a potent virulence mechanism [50].…”

“…Interestingly, OMVs serve as secretory vehicles by which pathogens not only modulate the host immune response, but also deliver toxins into host cells and are, thus, considered as a potent virulence mechanism [50]. In this light, the identified microRNA-size molecules may function as novel bacterial signalling molecules that mediate both the bacteria-eukaryotic host and bacteria-bacteria interactions during infection [21,22,49]. …”