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

Katja Koeppen, Thomas H. Hampton, Michael Jarek, Maren Scharfe, Scott A. Gerber, Daniel W. Mielcarz, Elora G. Demers, Emily L. Dolben, John H. Hammond, Deborah A. Hogan, Bruce A. Stanton, Marvin Whiteley
2016 PLoS Pathogens  
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
more » ... 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. Author Summary Pseudomonas aeruginosa is a gram-negative, opportunistic pathogen that accounts for about 10% of all hospital-acquired infections in the US and primarily infects immunocompromised hosts, including patients 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 sRNA contained inside OMVs secreted by P. aeruginosa.
doi:10.1371/journal.ppat.1005672 pmid:27295279 pmcid:PMC4905634 fatcat:6gpnypy6mvapxg6js4iyxfvp6m