Fig. 5.

Staphylococcus aureus-generated deoxyadenosine kills macrophages by targeting the purine salvage pathway. Survival of U937 cells (A) and U937-derived macrophages (B) and their ADK^−/−, DCK^−/−, or SLC29A1^−/− variants following treatment with culture medium (RPMI) that had been conditioned by incubation with either wild-type S. aureus Newman or its nuc or adsA mutants in the presence of host DNA or dipyridamole (Dipy) (10 μM) as indicated with + and − signs. Data are the mean (±SD) of three independent determinations. Statistically significant differences were analyzed with one-way ANOVA and Bonferroni’s multiple comparison test and with the Student’s t test for the ±Dipy experiment. ns, not significant (P > 0.05); **P < 0.01; ***P < 0.001. (C) Diagram illustrating S. aureus killing of macrophages via hENT1-mediated uptake of AdsA/Nuc-derived dAdo, ADK/DCK-catalyzed conversion of dAdo to dAMP, as well as subsequent conversions to dADP and dATP, triggering caspase-3 activation and macrophage apoptosis.