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 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.
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Katja
K
Koeppen
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Thomas H
TH
Hampton
Genome Analytics Helmholtz Centre for Infection Research, Braunschweig, Lower Saxony, Germany.
Michael
M
Jarek
Genome Analytics Helmholtz Centre for Infection Research, Braunschweig, Lower Saxony, Germany.
Maren
M
Scharfe
Departments of Genetics and Biochemistry, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.|Norris Cotton Cancer Center, Lebanon, New Hampshire, United States of America.
Scott A
SA
Gerber
Norris Cotton Cancer Center, Lebanon, New Hampshire, United States of America.
Daniel W
DW
Mielcarz
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Elora G
EG
Demers
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Emily L
EL
Dolben
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
John H
JH
Hammond
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Deborah A
DA
Hogan
Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Bruce A
BA
Stanton
D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D040901:Proteomics; D011552:Pseudomonas Infections; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity; D034741:RNA, Small Interfering / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000382:microbiology; D022161:Transport Vesicles / Q000235:genetics / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D034741:RNA, Small Interfering; D012367:RNA, Viral