Chronic Staphylococcus aureus Lung Infection Correlates With Proteogenomic and Metabolic Adaptations Leading to an Increased Intracellular Persistence

Autor: Agnès Ferroni, Alain Charbit, Fabiola Tros, Xavier Nassif, Ida Chiara Guerrera, Daniel Euphrasie, Mathieu Coureuil, Ivan Nemanzny, Cerina Chhuon, Elodie Ramond, Isabelle Sermet-Gaudelus, Julie Meyer, Anne Jamet, Marion Dupuis, Xin Tan
Přispěvatelé: Charbit, Alain, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Canalopathies épithéliales: la mucoviscidose et autres maladies, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Rok vydání: 2019
Předmět:
Proteomics
0301 basic medicine
Microbiology (medical)
Staphylococcus aureus
medicine.drug_class
030106 microbiology
Antibiotics
Virulence
Biology
medicine.disease_cause
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
Cystic fibrosis
biofilm
Cell Line
Persistence (computer science)
Microbiology
cystic fibrosis
03 medical and health sciences
Tandem Mass Spectrometry
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
medicine
Humans
Pathogen
Cells
Cultured
Proteogenomics
030304 developmental biology
0303 health sciences
Lung
030306 microbiology
business.industry
Biofilm
intracellular persistence
medicine.disease
Adaptation
Physiological
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Anti-Bacterial Agents
3. Good health
proteogenomics
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Biofilms
[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases
[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
business
Intracellular
Chromatography
Liquid
Zdroj: Clinical Infectious Diseases
Clinical Infectious Diseases, 2019, 69 (11), pp.1937-1945. ⟨10.1093/cid/ciz106⟩
Clinical Infectious Diseases, Oxford University Press (OUP), 2019, 69 (11), pp.1937-1945. ⟨10.1093/cid/ciz106⟩
ISSN: 1537-6591
1058-4838
DOI: 10.1093/cid/ciz106
Popis: BackgroundChronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood.MethodsWe selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence.ResultsFor the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated.Furthermore, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets.ConclusionsOur results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.SummaryS. aureus persists for years in the lungs of patients with cystic fibrosis despite antibiotic therapies. We demonstrate that S. aureus adaptation leads to increased intracellular persistence suggesting a key role for intracellular niche during S. aureus chronic lung infection.
Databáze: OpenAIRE
Externí odkaz: