
@article {111547,
	title = {Active APPL1 sequestration by Plasmodium favors liver-stage development.},
	journal = {Cell Rep},
	volume = {39},
	year = {2022},
	month = {2022 May 31},
	pages = {110886},
	abstract = {<p>Intracellular pathogens manipulate host cells to survive and thrive. Cellular sensing and signaling pathways are among the key host machineries deregulated to favor infection. In this study, we show that liver-stage Plasmodium parasites compete with the host to sequester a host endosomal-adaptor protein (APPL1) known to regulate signaling in response to endocytosis. The enrichment of APPL1 at the parasitophorous vacuole membrane (PVM) involves an atypical Plasmodium Rab5 isoform (Rab5b). Depletion of host APPL1 alters neither the infection nor parasite development; however, upon overexpression of a GTPase-deficient host Rab5 mutant (hRab5_Q79L), the parasites are smaller and their PVM is stripped of APPL1. Infection with the GTPase-deficient Plasmodium berghei Rab5b mutant (PbRab5b_Q91L) in this case rescues the PVM APPL1 signal and parasite size. In summary, we observe a robust correlation between the level of APPL1 retention at the PVM and parasite size during exoerythrocytic development.</p>
},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2022.110886},
	author = {Lahree, Aparajita and Baptista, Sara de Jesus Santos and Marques, Sofia and Perschin, Veronika and Zuzarte-Lu{\'\i}s, Vanessa and Goel, Manisha and Choudhary, Hadi Hasan and Mishra, Satish and Stigloher, Christian and Zerial, Marino and Sundaramurthy, Varadharajan and Mota, Maria M}
}
@article {85902,
	title = {Disrupting Plasmodium UIS3-host LC3 interaction with a small molecule causes parasite elimination from host cells.},
	journal = {Commun Biol},
	volume = {3},
	year = {2020},
	month = {2020 Nov 19},
	pages = {688},
	abstract = {<p>The malaria parasite Plasmodium obligatorily infects and replicates inside hepatocytes surrounded by a parasitophorous vacuole membrane (PVM), which is decorated by the host-cell derived autophagy protein LC3. We have previously shown that the parasite-derived, PVM-resident protein UIS3 sequesters LC3 to avoid parasite elimination by autophagy from hepatocytes. Here we show that a small molecule capable of disrupting this interaction triggers parasite elimination in a host cell autophagy-dependent manner. Molecular docking analysis of more than 20 million compounds combined with a phenotypic screen identified one molecule, C4 (4-{[4-(4-{5-[3-(trifluoromethyl) phenyl]-1,2,4-oxadiazol-3-yl}benzyl)piperazino]carbonyl}benzonitrile), capable of impairing infection. Using biophysical assays, we established that this impairment is due to the ability of C4 to disrupt UIS3-LC3 interaction, thus inhibiting the parasite{\textquoteright}s ability to evade the host autophagy response. C4 impacts infection in autophagy-sufficient cells without harming the normal autophagy pathway of the host cell. This study, by revealing the disruption of a critical host-parasite interaction without affecting the host{\textquoteright}s normal function, uncovers an efficient anti-malarial strategy to prevent this deadly disease.</p>
},
	issn = {2399-3642},
	doi = {10.1038/s42003-020-01422-1},
	author = {Setua, Sonali and Enguita, Francisco J and Chora, {\^A}ngelo Ferreira and Ranga-Prasad, Harish and Lahree, Aparajita and Marques, Sofia and Sundaramurthy, Varadharajan and Mota, Maria M}
}
