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Tobramycin reduces key virulence determinants in the proteome of Pseudomonas aeruginosa outer membrane vesicles.
Koeppen, Katja; Barnaby, Roxanna; Jackson, Angelyca A; Gerber, Scott A; Hogan, Deborah A; Stanton, Bruce A.
Afiliación
  • Koeppen K; Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
  • Barnaby R; Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
  • Jackson AA; Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
  • Gerber SA; Department of Molecular and Systems Biology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
  • Hogan DA; Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
  • Stanton BA; Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
PLoS One ; 14(1): e0211290, 2019.
Article en En | MEDLINE | ID: mdl-30682135
Tobramycin is commonly used to treat Pseudomonas aeruginosa lung infections in patients with Cystic Fibrosis (CF). Tobramycin treatment leads to increased lung function and fewer clinical exacerbations in CF patients, and modestly reduces the density of P. aeruginosa in the lungs. P. aeruginosa resides primarily in the mucus overlying lung epithelial cells and secretes outer membrane vesicles (OMVs) that diffuse through the mucus and fuse with airway epithelial cells, thus delivering virulence factors into the cytoplasm that modify the innate immune response. The goal of this study was to test the hypothesis that Tobramycin reduces the abundance of virulence factors in OMVs secreted by P. aeruginosa. Characterization of the proteome of OMVs isolated from control or Tobramycin-exposed P. aeruginosa strain PAO1 revealed that Tobramycin reduced several OMV-associated virulence determinants, including AprA, an alkaline protease that enhances P. aeruginosa survival in the lung, and is predicted to contribute to the inhibitory effect of P. aeruginosa on Phe508del-CFTR Cl- secretion by primary human bronchial epithelial cells. Deletion of the gene encoding AprA reduced the inhibitory effect of P. aeruginosa on Phe508del-CFTR Cl- secretion. Moreover, as predicted by our proteomic analysis, OMVs isolated from Tobramycin treated P. aeruginosa had a diminished inhibitory effect on Phe508del-CFTR Cl- secretion compared to OMVs isolated from control P. aeruginosa. Taken together, our proteomic analysis of OMVs and biological validation suggest that Tobramycin may improve lung function in CF patients infected with P. aeruginosa by reducing several key virulence factors in OMVs that reduce CFTR Cl- secretion, which is essential for bacterial clearance from the lungs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Tobramicina / Exopeptidasas / Vesículas Secretoras / Proteómica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Tobramicina / Exopeptidasas / Vesículas Secretoras / Proteómica Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos