Cathepsin B gene disruption induced Leishmania donovani proteome remodeling implies cathepsin B role in secretome regulation.
Leishmania cysteine proteases are potential vaccine candidates and drug targets. To study the role of cathepsin B cysteine protease, we have generated and characterized cathepsin B null mutant L. donovani parasites. L. donovani cathepsin B null mutants grow normally in culture, but they show significantly attenuated virulence inside macrophages. Quantitative proteome profiling of wild type and null mutant parasites indicates cathepsin B disruption induced remodeling of L. donovani proteome. We identified 83 modulated proteins, of which 65 are decreased and 18 are increased in the null mutant parasites, and 66% (55/83) of the modulated proteins are L. donovani secreted proteins. Proteins involved in oxidation-reduction (trypanothione reductase, peroxidoxins, tryparedoxin, cytochromes) and translation (ribosomal proteins) are among those decreased in the null mutant parasites, and most of these proteins belong to the same complex network of proteins. Our results imply virulence role of cathepsin B via regulation of Leishmania secreted proteins.
Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada.
Teklu Kuru
TK
Gerbaba
Lashitew
L
Gedamu
D002401:Cathepsin B / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007893:Leishmania donovani / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity*; D008264:Macrophages / Q000469:parasitology; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis; D020543:Proteome / Q000235:genetics* / Q000378:metabolism; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D014774:Virulence
D020543:Proteome; D015800:Protozoan Proteins; D002401:Cathepsin B