Processment of plasmatic proteins by Plasmodium

• Grant number: 11/14403-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2011
• End date: September 30, 2015
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Adriana Karaoglanovic Carmona
• Grantee: Pollyana Maria Saud Melo
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 10/51423-0 - Bioactive peptides and peptidases: biological and immunobiological activities in infectious diseases and cancer, AP.TEM

Abstract

Malaria is a disease caused by Plasmodium parasites and remains one of the most prevalent and persistent infections affecting hundreds of million of people. It is a major socio-economic concern as thirty percent of the world population lives in endemics areas. The symptoms of malaria include the classic periodic fever, severe anemia, dysfunction in coagulation, inflammation and hemodynamics alterations in the host. The plasminogen and the kininogen are two host proteins that are involved in these processes, through formation of plasmin/angiostatin and bradykinin, respectively. Parasites proteases were described in invasion, egress of erythrocytes and degradation of host proteins. However, the processment of these proteins by parasites has not been thoroughly studied. Our group showed that malaria parasites are able to hydrolyze these two proteins and generate active fragments, which may modulate the parasites environment and other traits of the diseases. The roles of these peptides in the parasite-host interaction are still unclear. The aim of the present project is to evaluate the function of these generated peptides in the parasitism, focusing on cytoadherence and inflammation modulation by the parasite. The understanding of these pathways is important for the development of new drugs and the design of new treatment strategies, knowing that the emergence of multiresistant parasites hardens the control of this disease. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GONZALEZ-BACERIO, JORGE; MALUF, SARAH EL CHAMY; MENDEZ, YANIRA; PASCUAL, ISEL; FLORENT, ISABELLE; MELO, POLLYANA M. S.; BUDU, ALEXANDRE; FERREIRA, JULIANA C.; MORENO, ERNESTO; CARMONA, ADRIANA K.; et al. KBE009: An antimalarial bestatin-like inhibitor of the Plasmodium falciparum M1 aminopeptidase discovered in an Ugi multicomponent reaction-derived peptidomimetic library. Bioorganic & Medicinal Chemistry, v. 25, n. 17, p. 4628-4636, SEP 1 2017. (11/14403-4, 13/12913-0)

MELO, POLLYANA M. S.; MALUF, SARAH EL CHAMY; AZEVEDO, MAURO F.; PASCHOALIN, THAYSA; BUDU, ALEXANDRE; BAGNARESI, PIERO; HENRIQUE-SILVA, FLAVIO; SOARES-COSTA, ANDREA; GAZARINI, MARCOS L.; CARMONA, ADRIANA K.. Inhibition of Plasmodium falciparum cysteine proteases by the sugarcane cystatin CaneCPI-4. Parasitology International, v. 67, n. 2, p. 233-236, APR 2018. (15/06861-3, 15/19316-3, 16/15298-3, 11/14403-4, 13/12913-0, 09/53840-0)

BUDU, ALEXANDRE; GOMES, MAYRIM M.; MELO, POLLYANA M.; MALUF, SARAH EL CHAMY; BAGNARESI, PIERO; AZEVEDO, MAURO F.; CARMONA, ADRIANA K.; GAZARINI, MARCOS L.. Calmidazolium evokes high calcium fluctuations in Plasmodium falciparum. CELLULAR SIGNALLING, v. 28, n. 3, p. 125-135, MAR 2016. (11/14403-4, 13/12913-0, 15/07182-2)