Functional Analysis of the Cathepsin-Like Cysteine Protease Genes in Adult Brugia malayi Using RNA Interference

Ford, Louise, Zhang, J., Liu, J., Hashmi, S., Fuhrman, J. A., Oksov, Y. and Lustigman, S. (2009) 'Functional Analysis of the Cathepsin-Like Cysteine Protease Genes in Adult Brugia malayi Using RNA Interference'. PLoS Neglected Tropical Diseases, Vol 3, Issue 2, e377.

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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.

Methods and Findings

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.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids WA Public Health > WA 30 Socioeconomic factors in public health (General) QW Microbiology and Immunology > Immune Responses > QW 700 Infection. Mechanisms of infection and resistance. QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 806 Vaccination WC Communicable Diseases > Tropical and Parasitic Diseases > WC 755 Epidemiology WA Public Health > Health Problems of Special Population Groups > WA 395 Health in developing countries WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General) QX Parasitology > QX 4 General works QX Parasitology > Helminths. Annelida > QX 203 Nematoda QX Parasitology > QX 45 Host-parasite relations
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pntd.0000377
Depositing User:	Mary Creegan
Date Deposited:	01 Jun 2010 17:31
Last Modified:	06 Feb 2018 12:59
URI:	https://archive.lstmed.ac.uk/id/eprint/268

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