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Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that (\n                    <jats:italic>R<\/jats:italic>\n                    )-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (\n                    <jats:italic>R<\/jats:italic>\n                    )-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (\n                    <jats:italic>R<\/jats:italic>\n                    )-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.\n                  <\/jats:p>","DOI":"10.7554\/elife.91157","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T11:48:27Z","timestamp":1697024907000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.91157","source":"Crossref","is-referenced-by-count":2,"title":["Targeting host deoxycytidine kinase mitigates Staphylococcus aureus abscess formation"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3248-2572","authenticated-orcid":true,"given":"Volker","family":"Winstel","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04bya8j72","id-type":"ROR","asserted-by":"publisher"}],"name":"Research Group Pathogenesis of Bacterial Infections; TWINCORE, Centre for Experimental and 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