@article{0cc5f6b76dd94d519c539730da91dd83,
title = "Distinct physiological states of Plasmodium falciparum in malaria-infected patients",
abstract = "Infection with the malaria parasite Plasmodium falciparum leads to widely different clinical conditions in children, ranging from mild flu-like symptoms to coma and death. Despite the immense medical implications, the genetic and molecular basis of this diversity remains largely unknown. Studies of in vitro gene expression have found few transcriptional differences between different parasite strains. Here we present a large study of in vivo expression profiles of parasites derived directly from blood samples from infected patients. The in vivo expression profiles define three distinct transcriptional states. The biological basis of these states can be interpreted by comparison with an extensive compendium of expression data in the yeast Saccharomyces cerevisiae. The three states in vivo closely resemble, first, active growth based on glycolytic metabolism, second, a starvation response accompanied by metabolism of alternative carbon sources, and third, an environmental stress response. The glycolytic state is highly similar to the known profile of the ring stage in vitro, but the other states have not been observed in vitro. The results reveal a previously unknown physiological diversity in the in vivo biology of the malaria parasite, in particular evidence for a functional mitochondrion in the asexual-stage parasite, and indicate in vivo and in vitro studies to determine how this variation may affect disease manifestations and treatment.",
author = "Daily, {J. P.} and D. Scanfeld and N. Pochet and {Le Roch}, K. and D. Plouffe and M. Kamal and O. Sarr and S. Mboup and O. Ndir and D. Wypij and K. Levasseur and E. Thomas and P. Tamayo and C. Dong and Y. Zhou and Lander, {E. S.} and D. Ndiaye and D. Wirth and Winzeler, {E. A.} and Mesirov, {J. P.} and A. Regev",
note = "Funding Information: Acknowledgements We thank the villagers and health care workers in Velingara, Senegal, for their participation in and support of this project; T. Taylor for critical advice and encouragement; G. Chechik, N. Barkai and O. Rando for providing parts of the compiled expression compendium for S. cerevisiae; and J. Bistline for assistance with the figures. J.P.D. is supported by the National Institute of Allergy and Infectious Diseases. N.P. is a Henri Benedictus Fellow of the King Baudouin Foundation and the Belgian American Educational Foundation. P.T. is supported by the National Institutes of Health (NIH). D.F.W. is supported by the Ellison Medical Foundation, the NIH, the Exxon Mobil Foundation and the Harvard School of Public Health. E.A.W. is supported by the Keck Foundation, the Novartis Research Foundation and the NIH. J.P.M. and D.S. are supported by the NIH and the National Science Foundation. A.R. is supported by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund. The field work was supported by the Fogarty International from the NIH, the NIH Malaria Diversity grant, the Exxon Mobil Foundation, the Ellison Medical Foundation, the Burroughs–Welcome Fund and the Broad Institute of MIT and Harvard.",
year = "2007",
month = dec,
day = "13",
doi = "10.1038/nature06311",
language = "English (US)",
volume = "450",
pages = "1091--1095",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7172",
}