Targeting Leishmania donovani Sphingosine Kinase 1 using PF-543 enhances immune response and limits parasite load

PF-543 exerts moderate direct inhibition of parasite SphK1 while prominently modulating host SphK1-dependent immune and apoptotic pathways, collectively restricting Leishmania survival. Rather than functioning as a parasite-selective inhibitor, PF-543 acts as a dual host-parasite modulator. These findings provide proof-of-concept evidence that simultaneous targeting of sphingolipid signalling in both host and parasite can enhance anti-leishmanial efficacy and support further exploration of SphK-based combination therapeutic strategies.