{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Winstel V"],"funding":["Deutsche Forschungsgemeinschaft","NCI NIH HHS","National Institutes of Health","University of California, Los Angeles","NIH HHS"],"pagination":["RP91157"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10957174"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["12"],"pubmed_abstract":["Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. 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 (<i>R</i>)-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates <i>Staphylococcus aureus</i> abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (<i>R</i>)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (<i>R</i>)-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."],"journal":["eLife"],"pubmed_title":["Targeting host deoxycytidine kinase mitigates <i>Staphylococcus aureus</i> abscess formation."],"pmcid":["PMC10957174"],"funding_grant_id":["T32CA009120","WI4582/2-1","1R01CA260678-01","T32 CA009120","R01 CA260678","1R01CA25052901A1"],"pubmed_authors":["Winstel V","Le TM","Abt ER","Radu CG"],"additional_accession":[]},"is_claimable":false,"name":"Targeting host deoxycytidine kinase mitigates <i>Staphylococcus aureus</i> abscess formation.","description":"Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. 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 (<i>R</i>)-DI-87, a clinical-stage anticancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates <i>Staphylococcus aureus</i> abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (<i>R</i>)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (<i>R</i>)-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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2025-04-04T20:07:10.209Z","creation":"2025-04-04T20:07:10.209Z"},"accession":"S-EPMC10957174","cross_references":{"pubmed":["38512723"],"doi":["10.7554/eLife.91157"]}}