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Staphylococcus aureus targets the purine salvage pathway to kill phagocytes [Microbiology]

Immune evasion by the human pathogen Staphylococcus aureus includes the synthesis of cytotoxic deoxyadenosine (dAdo) from neutrophil extracellular traps to eliminate macrophages. The signaling pathway that triggers dAdo-mediated apoptosis in macrophages is not known. By using a genome-wide CRISPR-Cas9 knockout screen, we demonstrate that S. aureus -derived dAdo targets the purine salvage pathway to provoke caspase-3–dependent cell death in human macrophages, thereby antagonizing host immune responses and promoting the establishment of invasive disease. Interference with the staphylococcal dAdo signaling pathway may boost macrophage survival and phagocytic clearance of bacteria, providing new strategies for the treatment of S. aureus infections.

Authors:   Volker Winstel; Dominique Missiakas; Olaf Schneewind
Journal:   Proceedings of the National Academy of Sciences current issue
Volume:   115
edition:   26
Year:   2018
Pages:   6846
DOI:   10.1073/pnas.1805622115
Publication date:   26-Jun-2018
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