科學(xué)家首次提供了證據(jù)表明瘧原蟲在人體宿主不斷變化的環(huán)境中的發(fā)育與在更穩(wěn)定的實驗室環(huán)境中的發(fā)育明顯不同,。
他們的這項研究成果11月29日發(fā)表在了《自然》雜志的網(wǎng)站上,，這可能有助于解釋為什么有一些患者的癥狀比其他人的癥狀更嚴重。
來自塞內(nèi)加爾和美國的科學(xué)家篩查了塞內(nèi)加爾東部Velingara醫(yī)院的一些患者,，瘧疾在這個地區(qū)的流行程度很高,。他們收集了來自43名不同年齡和癥狀的兒童的血樣。
塞內(nèi)加爾達喀爾Le Dantec教學(xué)醫(yī)院的Daouda Ndiaye是該研究的共同作者之一,，他說,，他們對這些血樣中的惡性瘧原蟲進行了遺傳分析，發(fā)現(xiàn)了每一個人體宿主對瘧原蟲的生理都有影響,，而且可能對其毒力有影響,。
這組科學(xué)家寫道，瘧原蟲生物學(xué)在活的生物體內(nèi)具有“此前未知的生理多樣性”,。
Ndiaye說：“這是一個名副其實的進展,。盡管只研究了43名患者的樣本，我們發(fā)現(xiàn)了瘧原蟲的兩個新的生物狀態(tài),。”他們發(fā)現(xiàn)瘧原蟲可以活躍地生長,、忍受饑餓或者感受壓力，而只有第一種情況在實驗室培養(yǎng)的情況下能觀察到,。
美國加州諾華研究基金會基因組學(xué)研究所的Elizabeth Winzeler是論文的作者之一,，她說科學(xué)家此前在實驗室觀察的基礎(chǔ)上認定了瘧原蟲的新陳代謝，這與人體宿主內(nèi)部變化的環(huán)境不一樣,。
她告訴本網(wǎng)站說：“該研究標明,，我們可能不應(yīng)該這樣假定,。瘧原蟲在人體內(nèi)的生理狀況可能不同于在實驗室容器中瘧原蟲的生理。這項工作可能解釋為什么有些藥物在治愈瘧疾方面的效果并不像人們認為的那樣好,。”
Winzeler還說,，這項研究將有助于瘧疾藥物的開發(fā)，并提高開發(fā)瘧疾疫苗的可能性,。“這可能導(dǎo)致更有效的藥物組合,，同時針對［人體宿主和實驗室環(huán)境下的］各種生理狀態(tài)。更好的藥物組合將減少出現(xiàn)耐藥性的威脅,。”
原始出處:
Nature advance online publication 28 November 2007 | doi:10.1038/nature06311; Received 17 May 2007; Accepted 26 September 2007; Published online 28 November 2007
Distinct physiological states of Plasmodium falciparum in malaria-infected patients
J. P. Daily1,3, D. Scanfeld4, N. Pochet4,5, K. Le Roch6, D. Plouffe7, M. Kamal4, O. Sarr8, S. Mboup8, O. Ndir9, D. Wypij2, K. Levasseur1, E. Thomas4, P. Tamayo4, C. Dong1, Y. Zhou7, E. S. Lander4,10,11, D. Ndiaye9, D. Wirth1, E. A. Winzeler7,12, J. P. Mesirov4,13 & A. Regev4,10,13
Department of Immunology and Infectious Disease,
Department of Biostatistics, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA
Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA
Broad Institute of Massachusetts Institute of Technology and Harvard University, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
FAS Center for Systems Biology, Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Department of Cell Biology and Neuroscience, 900 University Avenue, University of California, Riverside, California 92521, USA
Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA
Laboratory of Bacteriology and Virology,
Department of Parasitology and Mycology, Dantec Hospital, Cheikh Anta Diop University, Dakar, BP 5005, Senegal
Department of Biology, Massachusetts Institute of Technology, 31 Ames Street, Cambridge, Massachusetts 02139, USA
The Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA
Department of Cell Biology, The Scripps Research Institute, 10550 Torrey Pines Road, La Jolla, California 92037, USA
These authors contributed equally to this work.
Correspondence to: J. P. Mesirov4,13A. Regev4,10,13 Correspondence and requests for materials should be addressed to J.P.M. (Email: [email protected]) or A.R. (Email: [email protected]).
Infection with the malaria parasite Plasmodium falciparum leads to widely different clinical conditions in children, ranging from mild flu-like symptoms to coma and death1. Despite the immense medical implications, the genetic and molecular basis of this diversity remains largely unknown2. Studies of in vitro gene expression have found few transcriptional differences between different parasite strains3. 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.
