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

• Published in: Mucosal immunology Vol. 8; no. 2; pp. 362 - 371
• Main Authors: López-Collazo, E, Jurado, T, de Dios Caballero, J, Pérez-Vázquez, M, Vindel, A, Hernández-Jiménez, E, Tamames, J, Cubillos-Zapata, C, Manrique, M, Tobes, R, Máiz, L, Cantón, R, Baquero, F, Del Campo, R
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.03.2015
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Child, Preschool; Computational Biology; Cystic Fibrosis - immunology; Cystic Fibrosis - microbiology; Evolution, Molecular; Follow-Up Studies; Gene Expression Profiling; Genome, Bacterial; High-Throughput Nucleotide Sequencing; Humans; Immunity, Innate - genetics; Male; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Methicillin-Resistant Staphylococcus aureus - immunology; Microbial Sensitivity Tests; Monocytes - immunology; Monocytes - metabolism; Monocytes - microbiology; Phagocytosis - genetics; Phagocytosis - immunology; Staphylococcal Infections - drug therapy; Staphylococcal Infections - immunology; Staphylococcal Infections - microbiology; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1933-0219; 1935-3456
• DOI: 10.1038/mi.2014.73

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.