Center for Tropical and Emerging Global Diseases
University of Georgia
New vaccines to reduce disease and mortality caused by Plasmodium falciparum malaria are urgently needed. Most vaccines target a single life-cycle stage and confer modest protection. Kirtley et al. test whether multistage immunity can improve protection and provide some of the first evidence that ‘multistage’ vaccines should be pursued. Chester J Joyner, Amadis R Vivas, …
Although people living in malaria-endemic areas experience repeated infections with Plasmodium, the role of regulatory T (Treg) cells in recurrent malaria remains poorly understood. During a primary infection with Plasmodium, Treg cells suppress protective immunity by inhibiting germinal center (GC) reactions, thereby impeding the control of parasitemia. In contrast, memory Treg (mTreg) cells remaining after the clearance of initial Plasmodium infection …
A fused dihydropyrrolidino-pyrimidine hit with low lipophilicity and excellent ligand efficiency was identified in a biochemical screen of the Global Health Chemical Diversity Library (GHCDL) against Plasmodium lysyl-tRNA synthetase (KRS). Structure-guided lead optimization delivered analogues with potent parasite growth inhibition, excellent biochemical and cellular selectivity (>1000-fold), and oral efficacy in the malaria NOD-scid-IL2Rγnull (SCID) mouse model. Structural …
Due to the emergence of resistance to both artemisinin derivatives, and their partner drugs, new antimalarials are urgently needed. Ideally, new orally active antimalarials would not only engage new targets but also demonstrate a high barrier to resistance selection, and the ability to kill both proliferating rings and growth-arrested rings resulting from artemisinin exposure. In …
Malaria, caused by Plasmodium falciparum, remains a major global health challenge, with an estimated 263 million new infections and 597,000 deaths annually. Increasing resistance to current antimalarial drugs underscores the urgent need for new therapeutics that target novel pathways in the parasite. We previously reported a novel class of β-carboline antimalarials, exemplified by PRC1584, which demonstrated …
Tetrahydro-β-carboline 1 (MMV008138) controls growth of asexual blood-stage Plasmodium falciparum by inhibiting IspD, an enzyme in the MEP pathway for synthesis of a critical metabolite, isopentenyl pyrophosphate (IPP). We have previously investigated the structure activity relationship (SAR) of three of its four rings (B, C, and D). In this report we investigate the SAR of …
OSMAC (one strain many compounds) provides a convenient strategy to produce chemically diverse and novel natural products. In the study, the application of an OSMAC approach on a fungus Penicillium citrinum YSC-1 isolated from a medicinal plant Chloranthus japonicus, using different culture media, led to the isolation and identification of seven new spirooxindole alkaloids penicitrimicins …
Regulatory T cells (Tregs) can persist as memory cells (mTregs) in both infectious and non-infectious settings. However, their functional behavior, phenotypic stability, and suppressive properties upon antigen re-exposure remain poorly understood. Emerging evidence suggests that mTregs exhibit enhanced proliferation and suppressive capacity upon re-encountering the same antigen, a feature that may be critical in recurrent …