TY - JOUR
T1 - GLUT1-mediated glucose uptake plays a crucial role during Plasmodium hepatic infection
AU - Meireles, Patrícia
AU - Sales-Dias, Joana
AU - Andrade, Carolina M.
AU - Mello-Vieira, João
AU - Mancio-Silva, Liliana
AU - Simas, J. Pedro
AU - Staines, Henry M.
AU - Prudêncio, Miguel
N1 - Funding Information:
We are very grateful to Marc Sitbon and Julie Laval (Institut de Génétique Moléculaire de Montpellier CNRS-UMSF, France), and Vincent Petit and Sandra Moriceau (Metafora biosystems), for kindly providing the HRBD-EGFP peptide, to Hiromi Imamura (Graduate School of Biostudies, Kyoto University, Japan) for kindly providing the pRSET-AT1.03 plasmid, to Maria M. Mota (Instituto de Medicina Molecular, Portugal) for critically reviewing the manuscript, to Marta Miranda for help with the viral infections, to Ana Parreira and Filipa Teixeira for producing the various lines of P. berghei-infected mosquitoes and to the bioimaging and flow cytometry facilities of iMM Lisboa for technical support. This work was supported by the Fundação para a Ciência e Tecnologia (www.fct.pt, FCT, Portugal) through grants PTDC/SAU/MIC/117060/2010 and PTDC/SAU-MET/118199/2010 to MP and LMS, respectively. MP was sponsored by an Investigador FCT (2013) grant, PM by FCT fellowship SFRH/BD/71098/2010 and LMS by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement N. 242095 (EVIMalaR). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Publisher Copyright:
© 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Intracellular pathogens have evolved mechanisms to ensure their survival and development inside their host cells. Here, we show that glucose is a pivotal modulator of hepatic infection by the rodent malaria parasite Plasmodium berghei and that glucose uptake via the GLUT1 transporter is specifically enhanced in P. berghei-infected cells. We further show that ATP levels of cells containing developing parasites are decreased, which is known to enhance membrane GLUT1 activity. In addition, GLUT1 molecules are translocated to the membrane of the hepatic cell, increasing glucose uptake at later stages of infection. Chemical inhibition of GLUT1 activity leads to a decrease in glucose uptake and the consequent impairment of hepatic infection, both in vitro and in vivo. Our results reveal that changes in GLUT1 conformation and cellular localization seem to be part of an adaptive host response to maintain adequate cellular nutrition and energy levels, ensuring host cell survival and supporting P. berghei hepatic development.
AB - Intracellular pathogens have evolved mechanisms to ensure their survival and development inside their host cells. Here, we show that glucose is a pivotal modulator of hepatic infection by the rodent malaria parasite Plasmodium berghei and that glucose uptake via the GLUT1 transporter is specifically enhanced in P. berghei-infected cells. We further show that ATP levels of cells containing developing parasites are decreased, which is known to enhance membrane GLUT1 activity. In addition, GLUT1 molecules are translocated to the membrane of the hepatic cell, increasing glucose uptake at later stages of infection. Chemical inhibition of GLUT1 activity leads to a decrease in glucose uptake and the consequent impairment of hepatic infection, both in vitro and in vivo. Our results reveal that changes in GLUT1 conformation and cellular localization seem to be part of an adaptive host response to maintain adequate cellular nutrition and energy levels, ensuring host cell survival and supporting P. berghei hepatic development.
UR - http://www.scopus.com/inward/record.url?scp=84979982342&partnerID=8YFLogxK
U2 - 10.1111/cmi.12646
DO - 10.1111/cmi.12646
M3 - Article
C2 - 27404888
AN - SCOPUS:84979982342
SN - 1462-5814
VL - 19
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 2
M1 - e12646
ER -
