title: In vivo attenuation and genetic evolution of a ST247-SCCmecI MRSA clone after 13 years of pathogenic bronchopulmonary colonization in a patient with cystic fibrosis: implications of the innate immune response.
abstract: Methicillin-resistant Staphylococcus aureus (MRSA) causes chronic pulmonary infections in patients with cystic fibrosis (CF). This study tracks the 13-year evolution (1996-2009) of a single MRSA clone in a male patient with CF, evaluating both the host immunogenic response and the microbial variations. Whole-genome sequencing was performed for the initial (CF-96) and evolved (CF-09) isolates. The immunogenicity of CF-96 and CF-09 was evaluated by incubation with innate immune cells from healthy volunteers. We also studied the patient's innate immune response profile, cytokine production, expression of triggering receptor expressed on myeloid cells-1 (TREM-1), and phagocytosis. A total of 30 MRSA ST247-SCCmecI-pvl(-) isolates were collected, which evidenced a genome size reduction from the CF-96 ancestor to the evolved CF-09 strain. Up to six changes in the spa-type were observed over the course of the 13-year evolution. Cytokine production, TREM-1 expression, and phagocytosis were significantly lower for the healthy volunteer monocytes exposed to CF-09, compared with those exposed to CF-96. Patient monocytes exhibited a reduced inflammatory response when challenged with CF-09. Genetic changes in MRSA, leading to reduced immunogenicity and entry into the refractory state, may contribute to the attenuation of virulence and efficient persistence of the bacteria in the CF lung.
authors.affiliation: 1] Department of Tumor Immunology, IdiPAZ, Madrid, Spain [2] Innate Inmmunity Group, IdiPAZ and University Hospital La Paz, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: López-Collazo
authors.affiliation: Department of Tumor Immunology, IdiPAZ, Madrid, Spain.
authors.forename: T
authors.initials: T
authors.lastname: Jurado
authors.affiliation: Department of Microbiology, University Hospital Ramón y Cajal and IRYCIS, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: de Dios Caballero
authors.affiliation: Department of Microbial Community Modeling, National Biotechnology Center, CSIC, Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Pérez-Vázquez
authors.affiliation: Department of Microbial Community Modeling, National Biotechnology Center, CSIC, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Vindel
authors.affiliation: Department of Tumor Immunology, IdiPAZ, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Hernández-Jiménez
authors.affiliation: National Microbiology Center, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Tamames
authors.affiliation: Department of Tumor Immunology, IdiPAZ, Madrid, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Cubillos-Zapata
authors.affiliation: Oh no sequences! Research group, Era7 Bioinformatics, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Manrique
authors.affiliation: Oh no sequences! Research group, Era7 Bioinformatics, Granada, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Tobes
authors.affiliation: Cystic Fibrosis Unit, University Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Máiz
authors.affiliation: 1] National Microbiology Center, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain [2] Cystic Fibrosis Unit, University Hospital Ramón y Cajal, Madrid, Spain [3] Spanish Network for the Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Cantón
authors.affiliation: 1] National Microbiology Center, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain [2] CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Baquero
authors.affiliation: 1] National Microbiology Center, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain [2] CIBER en Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Del Campo
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D002675:Child, Preschool; D019295:Computational Biology; D003550:Cystic Fibrosis / Q000276:immunology* / Q000382:microbiology*; D019143:Evolution, Molecular; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D008826:Microbial Sensitivity Tests; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D014409:Tumor Necrosis Factor-alpha