title: Staphylococcus aureus proteases degrade lung surfactant protein A potentially impairing innate immunity of the lung.
abstract: The pulmonary surfactant is a complex mixture of lipids and proteins that is important for respiratory lung functions, which also provides the first line of innate immune defense. Pulmonary surfactant protein-A (SP-A) is a major surfactant component with immune functions with importance during Staphylococcus aureus infections that has been demonstrated in numerous studies. The current study showed that S. aureus can efficiently cleave the SP-A protein using its arsenal of proteolytic enzymes. This degradation appears to be mediated by cysteine proteases, in particular staphopain A (ScpA). The staphopain-mediated proteolysis of SP-A resulted in a decrease or complete abolishment of SP-A biological activity, including the promotion of S. aureus phagocytosis by neutrophils, aggregation of Gram-negative bacteria and bacterial cell adherence to epithelium. Significantly, ScpA has also efficiently degraded SP-A in complete bronchi-alveolar lavage fluid from human lungs. This indicates that staphopain activity in the lungs is resistant to protease inhibitors, thus suggesting that SP-A can be cleaved in vivo. Collectively, this study showed that the S. aureus protease ScpA is an important virulence factor that may impair innate immunity of the lungs.
authors.affiliation: Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Kantyka
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Pyrc
authors.forename: Milosz
authors.initials: M
authors.lastname: Gruca
authors.forename: Jan
authors.initials: J
authors.lastname: Smagur
authors.forename: Karolina
authors.initials: K
authors.lastname: Plaza
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Guzik
authors.forename: Slawomir
authors.initials: S
authors.lastname: Zeglen
authors.forename: Marek
authors.initials: M
authors.lastname: Ochman
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
mesh_terms: D003546:Cysteine Endopeptidases / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D011023:Pneumonia, Staphylococcal / Q000201:enzymology / Q000276:immunology*; D037662:Pulmonary Surfactant-Associated Protein A / Q000276:immunology* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D037662:Pulmonary Surfactant-Associated Protein A; D003546:Cysteine Endopeptidases; C501295:staphopain A protein, Staphylococcus aureus