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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of Plasmodium falciparum cysteine proteases by the sugarcane cystatin CaneCPI-4

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Melo, Pollyana M. S. [1] ; Maluf, Sarah El Chamy [1] ; Azevedo, Mauro F. [2] ; Paschoalin, Thaysa [1] ; Budu, Alexandre [1] ; Bagnaresi, Piero [1] ; Henrique-Silva, Flavio [3] ; Soares-Costa, Andrea [3] ; Gazarini, Marcos L. [2] ; Carmona, Adriana K. [1]
Total Authors: 10
[1] Univ Fed Sao Paulo, Dept Biofis, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Biociencias, Santos - Brazil
[3] Univ Fed Sao Carlos, Dept Genet & Evolucao, Sao Carlos, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: Parasitology International; v. 67, n. 2, p. 233-236, APR 2018.
Web of Science Citations: 6

Malaria is a disease caused by Plasmodium parasites that affects hundreds of millions of people. Plasmodium proteases are involved in invasion, erythrocyte egress and degradation of host proteins. Falcipains are well studied cysteine peptidases located in P. falciparum food vacuoles that participate in hemoglobin degradation. Cystatins are natural cysteine protease inhibitors that are implicated in a wide range of regulatory processes. Here, we report that a cystatin from sugarcane, CaneCPI-4, is selectively internalized into P. falciparum infected erythrocytes and is not processed by the parasite proteolytic machinery. Furthermore, we demonstrated the inhibition of P. falciparum cysteine proteases by CaneCPI-4, suggesting that it can exert inhibitory functions inside the parasites. The inhibition of the proteolytic activity of parasite cells is specific to this cystatin, as the addition of an anti-CaneCPI-4 antibody completely abolished the inhibition. We extended the studies to recombinant falcipain-2 and falcipain-3 and demonstrated that CaneCPI-4 strongly inhibits these enzymes, with IC50 values of 12 nM and 42 nM, respectively. We also demonstrated that CaneCPI-4 decreased the hemozoin formation in the parasites, affecting the parasitemia. Taken together, this study identified a natural molecule as a potential antimalarial that specifically targets falcipains and also contributes to a better understanding of macromolecule acquisition by Plasmodium falciparum infected RBCs. (AU)

FAPESP's process: 09/53840-0 - Fluorescence system for investigations of physiological and pathophysiological aspects in cellular models
Grantee:Adriana Karaoglanovic Carmona
Support type: Multi-user Equipment Program
FAPESP's process: 16/15298-3 - P. falciparum egress from the host cell: identification of new targets
Grantee:Mauro Ferreira de Azevedo
Support type: Scholarships in Brazil - Young Researchers
FAPESP's process: 11/14403-4 - Processment of plasmatic proteins by Plasmodium
Grantee:Pollyana Maria Saud Melo
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 15/19316-3 - Regulation of P. falciparum egress from the host cell: identification of new targets
Grantee:Mauro Ferreira de Azevedo
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 13/12913-0 - Calcium-calmodulin of Plasmodium falciparum: identification of ligands and participation in the host-parasite signalling
Grantee:Alexandre Budu
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 15/06861-3 - Role of kinins during experimental Plasmodium infection
Grantee:Pollyana Maria Saud Melo
Support type: Scholarships in Brazil - Post-Doctorate