科学家首次提供了证据表明疟原虫在人体宿主不断变化的环境中的发育与在更稳定的实验室环境中的发育明显不同。
他们的这项研究成果11月29日发表在了《自然》杂志的网站上，这可能有助于解释为什么有一些患者的症状比其他人的症状更严重。
来自塞内加尔和美国的科学家筛查了塞内加尔东部Velingara医院的一些患者，疟疾在这个地区的流行程度很高。他们收集了来自43名不同年龄和症状的儿童的血样。
塞内加尔达喀尔Le Dantec教学医院的Daouda Ndiaye是该研究的共同作者之一，他说，他们对这些血样中的恶性疟原虫进行了遗传分析，发现了每一个人体宿主对疟原虫的生理都有影响，而且可能对其毒力有影响。
这组科学家写道，疟原虫生物学在活的生物体内具有“此前未知的生理多样性”。
Ndiaye说：“这是一个名副其实的进展。尽管只研究了43名患者的样本，我们发现了疟原虫的两个新的生物状态。”他们发现疟原虫可以活跃地生长、忍受饥饿或者感受压力，而只有第一种情况在实验室培养的情况下能观察到。
美国加州诺华研究基金会基因组学研究所的Elizabeth Winzeler是论文的作者之一，她说科学家此前在实验室观察的基础上认定了疟原虫的新陈代谢，这与人体宿主内部变化的环境不一样。
她告诉本网站说：“该研究标明，我们可能不应该这样假定。疟原虫在人体内的生理状况可能不同于在实验室容器中疟原虫的生理。这项工作可能解释为什么有些药物在治愈疟疾方面的效果并不像人们认为的那样好。”
Winzeler还说，这项研究将有助于疟疾药物的开发，并提高开发疟疾疫苗的可能性。“这可能导致更有效的药物组合，同时针对［人体宿主和实验室环境下的］各种生理状态。更好的药物组合将减少出现耐药性的威胁。”
原始出处:
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: mesirov@broad.mit.edu) or A.R. (Email: aregev@broad.mit.edu).
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.
