
@article {73034,
	title = {Association of  With the Apical Domain of Hepatocytes Is Necessary for the Parasite{\textquoteright}s Liver Stage Development.},
	journal = {Front Cell Infect Microbiol},
	volume = {9},
	year = {2020},
	month = {2019},
	pages = {451},
	abstract = {<p>parasites undergo a dramatic transformation during the liver stage of their life cycle, amplifying over 10,000-fold inside infected hepatocytes within a few days. Such a rapid growth requires large-scale interactions with, and manipulations of, host cell functions. Whereas hepatocyte polarity is well-known to be critical for liver function, little is presently known about its involvement during the liver stage of development. Apical domains of hepatocytes are critical components of their polarity machinery and constitute the bile canalicular network, which is central to liver function. Here, we employed high resolution 3-D imaging and advanced image analysis of -infected liver tissues to show that the parasite associates preferentially with the apical domain of hepatocytes and induces alterations in the organization of these regions, resulting in localized changes in the bile canalicular architecture in the liver tissue. Pharmacological perturbation of the bile canalicular network by modulation of AMPK activity reduces the parasite{\textquoteright}s association with bile canaliculi and arrests the parasite development. Our findings using -infected liver tissues reveal a host- interaction at the level of liver tissue organization. We demonstrate for the first time a role for bile canaliculi, a central component of the hepatocyte polarity machinery, during the liver stage of development.</p>
},
	issn = {2235-2988},
	doi = {10.3389/fcimb.2019.00451},
	author = {Balasubramanian, Lakshmi and Zuzarte-Lu{\'\i}s, Vanessa and Syed, Tabish and Mullick, Debakshi and Deb, Saptarathi and Ranga-Prasad, Harish and Meissner, Jana and Almeida, Ana and Furstenhaupt, Tobias and Siddiqi, Kaleem and Prud{\^e}ncio, Miguel and Rodrigues, Cecilia M P and Mota, Maria and Sundaramurthy, Varadharajan}
}
@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}
}
