Sharma Shruti, Singh Gaganmeet, Chavan Hemantkumar D, Dey Chinmoy S
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)(2), Sector 67, S.A.S. Nagar, Punjab 160 062, India.
Exp Parasitol. 2009 Dec;123(4):369-76. doi: 10.1016/j.exppara.2009.08.003. Epub 2009 Aug 11.
Leishmania donovani, causative organism for visceral leishmaniasis, is responsible for considerable mortality and morbidity worldwide. Generation of drug-resistant variants continue to challenge the chemotherapy, the mainstay to fight the disease. The aim of current study was proteomic profiling of wild type (Ld-Wt) and arsenite-resistant (Ld-As20) L. donovani. Significant differences in protein profiles were observed between Ld-As20 and its parent Ld-Wt strain. Proteomic analysis of 158 spots from Ld-Wt and 144 spots from, Ld-As20 identified 77 and 74 protein entries, respectively, through MALDI-TOF/TOF based mass spectrometry and database search. A shift in the isoelectric point of few proteins was observed both in Ld-Wt and Ld-As20, which raises the possibility of continuous arsenite stress, resulting in the differences in the protein profiles of drug-resistant strain from its parent wild type strain. The comparative proteomic data holds the key for elucidation of the multifactorial and complex drug resistance mechanism, like arsenite resistance, in the parasite.
杜氏利什曼原虫是内脏利什曼病的致病生物体，在全球范围内导致了相当高的死亡率和发病率。耐药变体的产生持续对作为对抗该疾病主要手段的化疗构成挑战。当前研究的目的是对野生型（Ld-Wt）和抗亚砷酸盐（Ld-As20）的杜氏利什曼原虫进行蛋白质组分析。在Ld-As20与其亲本Ld-Wt菌株之间观察到了蛋白质谱的显著差异。通过基于基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF/TOF）的质谱分析和数据库搜索，对来自Ld-Wt的158个斑点和来自Ld-As20的144个斑点进行蛋白质组分析，分别鉴定出77个和74个蛋白质条目。在Ld-Wt和Ld-As20中均观察到少数蛋白质的等电点发生了变化，这增加了持续亚砷酸盐应激的可能性，导致耐药菌株与其亲本野生型菌株的蛋白质谱存在差异。比较蛋白质组学数据是阐明寄生虫中多因素和复杂耐药机制（如抗亚砷酸盐机制）的关键。
