Department of Biochemistry, Indian Institute of Science, Bangalore, India.
PLoS One. 2010 Mar 22;5(3):e9796. doi: 10.1371/journal.pone.0009796.
Trypanosoma evansi infections, commonly called 'surra', cause significant economic losses to livestock industry. While this infection is mainly restricted to large animals such as camels, donkeys and equines, recent reports indicate their ability to infect humans. There are no World Animal Health Organization (WAHO) prescribed diagnostic tests or vaccines available against this disease and the available drugs show significant toxicity. There is an urgent need to develop improved methods of diagnosis and control measures for this disease. Unlike its related human parasites T. brucei and T. cruzi whose genomes have been fully sequenced T. evansi genome sequence remains unavailable and very little efforts are being made to develop improved methods of prevention, diagnosis and treatment. With a view to identify potential diagnostic markers and drug targets we have studied the clinical proteome of T. evansi infection using mass spectrometry (MS).
METHODOLOGY/PRINCIPAL FINDINGS: Using shot-gun proteomic approach involving nano-lc Quadrupole Time Of Flight (QTOF) mass spectrometry we have identified over 160 proteins expressed by T. evansi in mice infected with camel isolate. Homology driven searches for protein identification from MS/MS data led to most of the matches arising from related Trypanosoma species. Proteins identified belonged to various functional categories including metabolic enzymes; DNA metabolism; transcription; translation as well as cell-cell communication and signal transduction. TCA cycle enzymes were strikingly missing, possibly suggesting their low abundances. The clinical proteome revealed the presence of known and potential drug targets such as oligopeptidases, kinases, cysteine proteases and more.
CONCLUSIONS/SIGNIFICANCE: Previous proteomic studies on Trypanosomal infections, including human parasites T. brucei and T. cruzi, have been carried out from lab grown cultures. For T. evansi infection this is indeed the first ever proteomic study reported thus far. In addition to providing a glimpse into the biology of this neglected disease, our study is the first step towards identification of diagnostic biomarkers, novel drug targets as well as potential vaccine candidates to fight against T. evansi infections.
伊氏锥虫病，通常被称为“苏拉”，给畜牧业造成了巨大的经济损失。虽然这种感染主要局限于骆驼、驴和马等大型动物，但最近的报告表明，它也有感染人类的能力。目前，世界动物卫生组织（WAHO）没有规定针对这种疾病的诊断测试或疫苗，现有的药物毒性很大。因此，迫切需要开发针对这种疾病的改进诊断方法和控制措施。与相关的人类寄生虫——布氏锥虫和克氏锥虫不同，它们的基因组已经完全测序，但伊氏锥虫的基因组序列仍然未知，而且很少有人致力于开发改进的预防、诊断和治疗方法。为了确定潜在的诊断标志物和药物靶点，我们使用质谱（MS）技术研究了伊氏锥虫感染的临床蛋白质组。
方法/主要发现：我们使用 shotgun 蛋白质组学方法，涉及纳升液相四极杆飞行时间（QTOF）质谱，鉴定了感染骆驼分离株的小鼠中伊氏锥虫表达的 160 多种蛋白质。基于同源性的搜索，从 MS/MS 数据中鉴定蛋白质，结果大部分匹配来自相关的锥虫物种。鉴定的蛋白质属于各种功能类别，包括代谢酶、DNA 代谢、转录、翻译以及细胞间通讯和信号转导。TCA 循环酶明显缺失，可能表明它们的丰度较低。临床蛋白质组揭示了存在已知和潜在的药物靶点，如寡肽酶、激酶、半胱氨酸蛋白酶等。
结论/意义：以前对锥虫感染的蛋白质组学研究，包括人类寄生虫布氏锥虫和克氏锥虫，都是在实验室培养的细胞中进行的。对于伊氏锥虫感染，这确实是迄今为止首次进行的蛋白质组学研究。除了提供对这种被忽视疾病生物学的深入了解外，我们的研究是鉴定诊断生物标志物、新型药物靶点以及潜在疫苗候选物以对抗伊氏锥虫感染的第一步。
