Subtilisin-like proteases in nematodes.
ABSTRACT Cleavage by subtilisin-like proteases (subtilases) is an essential step in post-translational processing of proteins found in organisms ranging from yeast to mammals. Our knowledge of the diversity of this protease family in nematodes is aided by the rapid increase in sequence information, especially from the Brugia malayi genome project. Genetic studies of the subtilases in Caenorhabitis elegans give valuable insight into the biological function of these proteases in other nematode species. In this review, we focus on the subtilases in filarial nematodes as well as other parasitic and free-living nematodes in comparison to what is known in C. elegans. Topics to be addressed include expansion and diversity of the subtilase gene family during evolution, enhanced complexity created by alternative RNA splicing, molecular and biochemical characterization of the different subtilases and the challenges of designing subtilase-specific inhibitors for parasitic nematodes.
SourceAvailable from: Etienne G J Danchin[Show abstract] [Hide abstract]
ABSTRACT: Proteases perform essential physiological functions in all living organisms. In parasitic helminths, they are of particular importance for tissue penetration, digestion of host tissues for nutrition, and evasion of host immune responses. The recent availability of the genome sequence of the nematode Meloidogyne incognita has allowed the analysis of the protease repertoire of this major crop pathogen. The M. incognita degradome consists of at least 334 proteases that are distributed into 43 families of the five known catalytic classes. Expression profiling identified protease genes with a differential transcript level between eggs and infective juveniles. Comparing the M. incognita degradome with those of five other nematodes showed discrepancies in the distribution of some protease families, including large expansion in some families, that could reflect specific aspects of the parasitic lifestyle of this organism. This comparative study should provide a framework for deciphering the diversity of protease-mediated functions in nematodes.Genomics 10/2010; 97(1):29-36. DOI:10.1016/j.ygeno.2010.10.002 · 2.79 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: 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. 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. 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.PLoS Neglected Tropical Diseases 02/2009; 3(2):e377. DOI:10.1371/journal.pntd.0000377 · 4.49 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The open reading frame PA1242 in the genome of Pseudomonas aeruginosa PAO1 encodes a putative protease belonging to the peptidase S8 family of subtilases. The respective enzyme termed SprP consists of an N-terminal signal peptide and a so-called S8 domain linked by a domain of unknown function (DUF). Presumably, this DUF domain defines a discrete class of Pseudomonas proteins as homologous domains can be identified almost exclusively in proteins of the genus Pseudomonas. The sprP gene was expressed in Escherichia coli and proteolytic activity was demonstrated. A P. aeruginosa ∆sprP mutant was constructed and its gene expression pattern compared to the wild-type strain by genome microarray analysis revealing altered expression levels of 218 genes. Apparently, SprP is involved in regulation of a variety of different cellular processes in P. aeruginosa including pyoverdine synthesis, denitrification, the formation of cell aggregates, and of biofilms.12/2013; DOI:10.1002/mbo3.150