Comparative degradome analysis of the human pathogens Cryptosporidium parvum and C. hominis

TOMÁS POKLÉPOVICH CARIDE; LUCAS LANNUTTI; MÓNICA FLORIN-CHRISTENSEN; LEONHARD SCHNITTGER

Conferencia; ISCB Latin America bioinformatics conference; 2016

Background: Peptidases have been shown to play a crucial role for the survival and/or virulence of apicomplexan pathogens like Toxoplasma, Plasmodium, Babesia, and Cryptosporidium. Due to their vital function and their highly conserved structure, they constitute promising drug targets and potential vaccine candidates. Results: As query, proteinase family holotypes (MEROPS) were used to search Cryptosporidium parvum and Cryptosporidium hominis genomes for their complete proteinase repertoires. In order to verify found and identify additional proteinases an Interproscan search against the Pfam and Interpro database was done. The combination of both strategies allowed determining the C. parvum- and C. hominis- degradome comprising of 138 and 131 proteinases, respectively. A similar distribution of catalytic types with metallopeptidases as the most frequent type in both species was observed. By using bidirectional best hit and consulting the OrthoMCL database, 127 ortholog pairs were found. The remaining 11 and 4 peptidases of C. parvum and C. hominis, respectively, were denominated species-specific. Presence of catalytic residues was analyzed suggesting that at least 89 and 65 functional peptidases are encoded by C. parvum and C. hominis, respectively. Peptidases containing signal peptide and transmembrane domains were also defined.Conclusions: We suggest that identified ortholog pairs may be inhibited by a single drug formulation and therefore represent critical and interesting therapeutic targets. In contrast, species-specific proteinases are likely associated with life cycle differences and could be useful for the development of differential molecular diagnostics. This study does facilitate a rational selection of peptidases for the development of therapeutic interventions.