Infestin 1R, an intestinal subtilisin inhibitor from Triatoma infestans able to impair mammalian cell invasion by Trypanosoma cruzi

Infestins are Kazal-type serine protease inhibitors described in the midgut of Triatoma infestans, Chagas disease vector. Of all infestins, only infestin 1R (INF1R) does not control host blood coagulation, due to its inhibitory specificity for chymotrypsin-like proteases. We further investigated the effect of INF1R on cell infection by Trypanosoma cruzi. The importance of INF1R reactive site to inhibit T. cruzi cell invasion was confirmed using 1RSFTI, a synthetic cyclic peptide containing the inhibitor reactive site region hybridized to the Sunflower Trypsin Inhibitor-1 (SFTI-1). Our results suggest that INF1R efficiently inhibited parasite cell invasion. For the first time, a serine protease inhibitor, derived from T. infestans, was shown to impair cell invasion by T. cruzi, representing possible new target in parasite cell invasion.

Infestins are Kazal-type serine protease inhibitors described in the midgut of Triatoma infestans, Chagas' disease vector. Among them, only infestin 1R (INF1R) does not control host blood coagulation because of its inhibitory specificity for chymotrypsin-like proteases. We further investigated the effect of INF1R in cell infection by Trypanosoma cruzi. The INF1R reactive site importance in T. cruzi cell invasion inhibition activity was confirmed using the 1RSFTI, a synthetic cyclic peptide containing the inhibitor reactive site region hybridized to the Sunflower Trypsin Inhibitor-1 (SFTI-1). Therefore, our results suggest that INF1R inhibitory activity was important to inhibit parasite cell invasion. For the first time, a serine protease inhibitor, derived from T. infestans was shown to impair cell invasion by T. cruzi and a possible new target in parasite cell invasion.Highlights► Infestins are derived from a large precursor mRNA encoding for seven Kazal-type domains. ► Only infestin 1R inhibits subtilisin and neutrophil elastase. ► Infestin 1R interfere in Trypanosoma cruzi cell invasion. ► INF1R reactive site is important for T. cruzi cell invasion. ► 1RSFTI, a synthetic cyclic peptide containing the INF1R reactive site region also inhibited T. cruzi cell invasion.