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- W4387527441 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 (R)-DI-87, a clinical-stage anti-cancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), attenuates the virulence of antibiotic-resistant Staphylococcus aureus in a mouse model of bloodstream infection. Mechanistically, (R)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (R)-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." @default.
- W4387527441 created "2023-10-12" @default.
- W4387527441 date "2023-10-11" @default.
- W4387527441 modified "2023-10-12" @default.
- W4387527441 title "Reviewer #1 (Public Review): Targeting host deoxycytidine kinase attenuates Staphylococcus aureus virulence" @default.
- W4387527441 doi "https://doi.org/10.7554/elife.91157.1.sa1" @default.
- W4387527441 hasPublicationYear "2023" @default.
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