Staphylococcus aureus adapts to exploit collagen-derived proline during chronic infection.

Autor: Urso A; Department of Pediatric Infectious Diseases, Columbia University, New York, NY, USA.; Department of Pharmacology, Columbia University, New York, NY, USA.; Department of Pediatrics, Columbia University, New York, NY, USA., Monk IR; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia., Cheng YT; Department of Pediatric Infectious Diseases, Columbia University, New York, NY, USA.; Department of Pediatrics, Columbia University, New York, NY, USA., Predella C; Department of Pediatrics, Columbia University, New York, NY, USA., Wong Fok Lung T; Department of Pharmacology, Columbia University, New York, NY, USA.; Department of Pediatrics, Columbia University, New York, NY, USA., Theiller EM; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Boylan J; Department of Pharmacology, Columbia University, New York, NY, USA.; Department of Pediatrics, Columbia University, New York, NY, USA., Perelman S; Department of Microbiology, New York University, New York, NY, USA., Baskota SU; Department of Pathology, Columbia University, New York, NY, USA., Moustafa AM; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA., Lohia G; Department of Pharmacology, Columbia University, New York, NY, USA.; Department of Pediatrics, Columbia University, New York, NY, USA., Lewis IA; Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada., Howden BP; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.; Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia., Stinear TP; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia., Dorrello NV; Department of Pediatrics, Columbia University, New York, NY, USA., Torres V; Department of Microbiology, New York University, New York, NY, USA., Prince AS; Department of Pediatric Infectious Diseases, Columbia University, New York, NY, USA. asp7@cumc.columbia.edu.; Department of Pharmacology, Columbia University, New York, NY, USA. asp7@cumc.columbia.edu.; Department of Pediatrics, Columbia University, New York, NY, USA. asp7@cumc.columbia.edu.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2024 Oct; Vol. 9 (10), pp. 2506-2521. Date of Electronic Publication: 2024 Aug 12.
DOI: 10.1038/s41564-024-01769-9
Abstrakt: Staphylococcus aureus is a pulmonary pathogen associated with substantial human morbidity and mortality. As vaccines targeting virulence determinants have failed to be protective in humans, other factors are likely involved in pathogenesis. Here we analysed transcriptomic responses of human clinical isolates of S. aureus from initial and chronic infections. We observed upregulated collagenase and proline transporter gene expression in chronic infection isolates. Metabolomics of bronchiolar lavage fluid and fibroblast infection, growth assays and analysis of bacterial mutant strains showed that airway fibroblasts produce collagen during S. aureus infection. Host-adapted bacteria upregulate collagenase, which degrades collagen and releases proline. S. aureus then imports proline, which fuels oxidative metabolism via the tricarboxylic acid cycle. Proline metabolism provides host-adapted S. aureus with a metabolic benefit enabling out-competition of non-adapted strains. These data suggest that clinical settings characterized by airway repair processes and fibrosis provide a milieu that promotes S. aureus adaptation and supports infection.
(© 2024. The Author(s).)
Databáze: MEDLINE
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