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

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 th...

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Vydáno v:	PLoS pathogens Ročník 12; číslo 6; s. e1005672
Hlavní autoři:	Koeppen, Katja, Hampton, Thomas H., Jarek, Michael, Scharfe, Maren, Gerber, Scott A., Mielcarz, Daniel W., Demers, Elora G., Dolben, Emily L., Hammond, John H., Hogan, Deborah A., Stanton, Bruce A.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Public Library of Science 01.06.2016 Public Library of Science (PLoS)
Témata:	Analysis Animals Antigens Bacteria Bacterial Outer Membrane Proteins - metabolism Biology and Life Sciences Cancer Chronic obstructive pulmonary disease Cystic fibrosis Cytokines Disease control Gene expression Gram-negative bacteria Grants Hospitals Host-Pathogen Interactions - physiology Humans Immune response Kinases Male Medicine and Health Sciences Membranes (Biology) Mice Mice, Inbred C57BL Mortality Nosocomial infections Pathogenic microorganisms Pathogens Polymerase Chain Reaction Proteomics Pseudomonas aeruginosa Pseudomonas aeruginosa - pathogenicity Pseudomonas Infections Research and analysis methods Respiratory Mucosa - microbiology RNA sequencing RNA, Small Interfering - metabolism RNA, Viral - metabolism Rodents Transport Vesicles - genetics Transport Vesicles - metabolism Viral infections United States > US
ISSN:	1553-7374, 1553-7366, 1553-7374
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 The authors have declared that no competing interests exist. Conceived and designed the experiments: KK THH MJ SAG ELD JHH DAH BAS. Performed the experiments: KK MS SAG DWM EGD ELD JHH. Analyzed the data: KK THH SAG DWM. Contributed reagents/materials/analysis tools: MJ MS SAG DWM EGD DAH BAS. Wrote the paper: KK THH SAG ELD JHH DAH BAS.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1005672