title: Functional analysis of the cathepsin-like cysteine protease genes in adult Brugia malayi using RNA interference.
abstract: BACKGROUND
  Cathepsin-like enzymes have been identified as potential targets for drug or vaccine development in many parasites, as their functions appear to be essential in a variety of important biological processes within the host, such as molting, cuticle remodeling, embryogenesis, feeding and immune evasion. Functional analysis of Caenorhabditis elegans cathepsin L (Ce-cpl-1) and cathepsin Z (Ce-cpz-1) has established that both genes are required for early embryogenesis, with Ce-cpl-1 having a role in regulating in part the processing of yolk proteins. Ce-cpz-1 also has an important role during molting.
  
  
  RESULTS
  RNA interference assays have allowed us to verify whether the functions of the orthologous filarial genes in Brugia malayi adult female worms are similar. Treatment of B. malayi adult female worms with Bm-cpl-1, Bm-cpl-5, which belong to group Ia of the filarial cpl gene family, or Bm-cpz-1 dsRNA resulted in decreased numbers of secreted microfilariae in vitro. In addition, analysis of the intrauterine progeny of the Bm-cpl-5 or Bm-cpl Pro dsRNA- and siRNA-treated worms revealed a clear disruption in the process of embryogenesis resulting in structural abnormalities in embryos and a varied differential development of embryonic stages.
  
  
  CONCLUSIONS
  Our studies suggest that these filarial cathepsin-like cysteine proteases are likely to be functional orthologs of the C. elegans genes. This functional conservation may thus allow for a more thorough investigation of their distinct functions and their development as potential drug targets.
authors.affiliation: Laboratory of Molecular Parasitology, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, United States of America. louise.ford@liverpool.ac.uk
authors.forename: Louise
authors.initials: L
authors.lastname: Ford
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Sarwar
authors.initials: S
authors.lastname: Hashmi
authors.forename: Juliet A
authors.initials: JA
authors.lastname: Fuhrman
authors.forename: Yelena
authors.initials: Y
authors.lastname: Oksov
authors.forename: Sara
authors.initials: S
authors.lastname: Lustigman
mesh_terms: D000818:Animals; D017178:Brugia malayi / Q000201:enzymology* / Q000235:genetics; D002403:Cathepsins / Q000235:genetics; D057056:Cysteine Proteases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D017238:Genes, Helminth / Q000235:genetics*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics
chemical_list: D012330:RNA, Double-Stranded; D002403:Cathepsins; D057056:Cysteine Proteases