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In vitro gene silencing of independent phosphoglycerate mutase (iPGM) in the filarial parasite Brugia malayi

Infectious Diseases of Poverty 2013年第1期2卷 27-38页

作者： Prashant Kumar Singh susheela kushwaha Shahab Mohd Manisha Pathak Shailja Misra-Bhattacharya Division of Parasitology CSIR-Central Drug Research InstituteB.S.10/1Sector 10Jankipuram ExtensionSitapur RoadLucknow 226021UPIndia

Background:The phosphoglycerate mutase(PGM)enzyme catalyzes the interconversion of 2-and 3-phosphoglycerate in the glycolytic/gluconeogenic pathways that are present in the majority of cellular *** can be classified as cofactor-dependent PGM(dPGM)or cofactor-independent PGM(iPGM).Vertebrates,yeasts,and many bacteria have only dPGM,while higher plants,nematodes,archaea,and many other bacteria have only iPGM.A small number of bacteria,including Escherichia coli and certain archaea and protozoa,contain both *** silencing of ipgm in Caenorhabditis elegans(***)has demonstrated the importance of this enzyme in parasite viability and,therefore,its potential as an anthelmintic drug *** this study,the role of the Brugia malayi(***)ipgm in parasite viability,microfilaria release,embryogenesis,and in vivo development of infective larvae post-gene silencing was explored by applying ribonucleic acid(RNA)interference ***:The in vitro ipgm gene silencing by small interfering RNA(siRNA)leads to severe phenotypic deformities in the intrauterine developmental stages of female worms with a drastic reduction(~90%)in the motility of adult parasites and a significantly reduced(80%)release of microfilariae(mf)by female worms in *** half of the in vitro-treated infective L3 displayed sluggish *** in vivo survival and development of siRNA-treated infective larvae(L3)was investigated in the peritoneal cavity of jirds where a~45%reduction in adult worm establishment was ***:The findings clearly suggest that iPGM is essential for both larval and adult stages of *** parasite and that it plays a pivotal role in female worm *** results thus validate the Bm-iPGM as a putative anti-filarial drug target.

关键词： siRNA Lymphatic filariasis Drug target RNAi Embryogenesis

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