{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:08:47Z","timestamp":1787962127961,"version":"build-2784847793"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T00:00:00Z","timestamp":1696204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> is a common cause of hospital-acquired pneumonia associated with high mortality. Adequate clinical treatment is impeded by increasing occurrence of antibiotic resistances. Understanding the underlying mechanisms of its virulence during infections is a prerequisite to finding alternative treatments. Here, we demonstrated that an increased nuclease activity of a <jats:italic>S. aureus<\/jats:italic> isolate from a person with cystic fibrosis confers a growth advantage in a model of acute lung infection compared to the isogenic strain with low nuclease activity. Comparing these CF-isolates with a common MRSA-USA300 strain with similarly high nuclease activity but significantly elevated levels of Staphylococcal Protein A (SpA) revealed that infection with USA300 resulted in a significantly increased bacterial burden in a model of murine lung infection. Replenishment with the cell wall-bound SpA of <jats:italic>S. aureus<\/jats:italic>, which can also be secreted into the environment and binds to tumor necrosis factor receptor -1 (TNFR-1) to the CF-isolates abrogated these differences. <jats:italic>In vitro<\/jats:italic> experiments confirmed significant differences in <jats:italic>spa<\/jats:italic>-expression between USA300 compared to CF-isolates, thereby influencing TNFR-1 shedding, L-selectin shedding, and production of reactive oxygen species through activation of ADAM17.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1259004","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T16:25:46Z","timestamp":1696263946000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Nuclease activity and protein A release of Staphylococcus aureus clinical isolates determine the virulence in a murine model of acute lung 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