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.
Highlights
Pseudomonas aeruginosa is a gram-negative, opportunistic pathogen that primarily infects immunocompromised hosts including cancer and AIDS patients, burn victims, patients on ventilators and individuals with chronic obstructive pulmonary disease and cystic fibrosis
Gram-negative bacteria like P. aeruginosa produce outer membrane vesicles (OMVs), which constitute an important mechanism for host colonization
In this study we demonstrate a novel mechanism of pathogen-host interaction that attenuates the innate immune response in human airway epithelial cells and in mouse lung through a regulatory short RNAs (sRNAs) contained inside OMVs secreted by P. aeruginosa
Summary
Pseudomonas aeruginosa is a gram-negative, opportunistic pathogen that primarily infects immunocompromised hosts including cancer and AIDS patients, burn victims, patients on ventilators and individuals with chronic obstructive pulmonary disease and cystic fibrosis. Like other gram-negative bacteria, P. aeruginosa produces outer membrane vesicles (OMVs), which constitute an important mechanism of interaction with hosts and competing bacterial strains in their natural environment [2,3]. OMVs are 50–250 nm spheroid particles derived from the outer membrane that are constitutively secreted and consist of lipids, proteins and lipopolysaccharide (LPS) [3]. OMVs of many gram-negative bacteria including P. aeruginosa contain DNA [4,5]. Distinct P. aeruginosa virulence factors like alkaline phosphatase, phospholipase Cs, β-lactamase and Cif (CFTR Inhibitory Factor) are differentially packaged and enriched in OMVs [11,12]. OMVs diffuse across mucus and fuse with airway epithelial cells releasing their cargo into host cells [11,13]
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