Several might play a role in the pathology. For instance, we identified two oligopeptidases. One (prolyl-oligopeptidase) was previously shown to be secreted by T. cruzi [41] and presumed to facilitate the infection of host cells by degrading the collagen of the extracellular

JNK inhibitor matrix. Oligopeptidase B is secreted from T. brucei and T. congolense [42, 43]. This enzyme is able to cleave host peptide hormones such as atrial natriuretic factor [44], thus contributing to the increase in blood volume [45] and possibly to the disruption of the blood-brain barrier [46], both associated with the infection. Other symptoms of trypanosomiasis, such as the perturbation of the endocrine rhythms [47], could also involve oligopeptidase B. More generally, GW-572016 chemical structure it can be speculated that oligopeptidases, by cleaving regulatory peptides, could play pleiotropic roles in the pathogenic process developed during HAT. In contrast, for M20-M25-M40 and M17 family peptidases, where evidence also exists for their secretion by other organisms [48, 49], the identification in the secretome of Trypanosoma is novel and it is too early to speculate on its functions. Table 1 Diversity of peptidase families

found in the secretome of T. brucei gambiense bloodstream form and their distribution in other organisms. Families of Peptidases Distribution Serine peptidase family S9 Bacteria, Archaea, Protozoa, Fungi, Plants, Animals, Viruse Cysteine peptidase family C2 Bacteria, ———-, Protozoa, Fungi, Plants, Animals, ——– Cysteine

peptidase family C13 Bacteria, Archaea, Protozoa, Fungi, Plants, Animals, ——– Cysteine peptidase family C19 Bacteria, ———-, Protozoa, Fungi, Plants, Animals, Viruse Metallo-peptidase family M1 Bacteria, Archaea, Protozoa, Fungi, Plants, Animals, ——– Metallo-peptidase family M3 Bacteria, Archaea, Protozoa, Fungi, Plants, Animals, ——– Metallo-peptidase family M16 Bacteria, Archaea, Protozoa, Fungi, Plants, Animals, Viruse Metallo-peptidase http://www.selleck.co.jp/products/Neratinib(HKI-272).html family M17 Bacteria, Archaea, Protozoa, Fungi, Plants, Animals, ——– Metallo-peptidase family M20 Bacteria, Archaea, Protozoa, Fungi, Plants, Animals, ——– Metallo-peptidase family M24 Bacteria, Archaea, Protozoa, Fungi, Plants, Animals, ——– Metallo-peptidase family M32 Bacteria, Archaea, Protozoa, ——-, Plants, ———-, ——– Among metallopeptidases, the thimet oligopeptidase A is the first member of the M3 family to be identified in Protozoa. Thus, this protease, which processes neuropeptides in humans [50], may be a good candidate for a specific diagnostic marker. Another metallopeptidase in the secretome belongs to the M32 family, absent in selleck compound eukaryotic genomes other than trypanosomatids [51]. Although of unknown biological function, it might offer attractive drug targets against Trypanosoma.