Schistosomiasis is a neglected tropical disease that ranks, with malaria and tuberculosis, as a major source of morbidity despite of strenuous control efforts. It is caused by blood flukes of the genus Schistosoma, which have complex life cycles comprising multiple morphologically distinct phenotypes in definitive human and intermediate snail hosts. S. mansoni, is one of the species that infects humans.
Praziquantel (PZQ), is almost exclusively used to treat the infection, but this does not prevent reinfection and with the large-scale control programs in place, the extensive use of PZQ for over 20 years in some African nations has raised concern regarding the selection of drug resistant worms.
This project aims to characterize the mechanisms and possible genetic markers involved in PZQ drug resistance in S. mansoni and analyze the role of ABC-transport inhibitors as resistance reversing agents and, thus, candidates to new anti-schistosomiasis drugs.
A project such as this with genomic sequencing and trancriptomic / proteomic analysis of sensitive versus resistant parasites will allow the detection of genes that encode proteins that are involved in key pathways for the metabolism of the parasites thus enabling (facilitating) the identification of new therapeutic targets for S. mansoni which, considering that schistosomiasis is a major neglected disease, is of great importance for the future. These new therapeutic targets would not only be very important for intestinal schistosomiasis and also for the vesical form as well as to other helminthiasis.
Improving the knowledge of parasitic proteome in the presence and the absence of PZQ (or any other drug) will always be an asset in the search for new therapeutic targets.
- URBACZEK AC, LEÃO PACC, DE SOUZA FZR, AFONSO A, ALBERICE JV, CAPPELINI LTD, CARLOS IZ, CARRILHO E. (2017) Endothelial Cell Culture Under Perfusion On A Polyester-Toner Microfluidic Device. Scientific Reports 7: 10466 IF e citações
- DE PAULA AD, BRUNETTO MMM, REZENDE MORAIS E, GRACIANO DE PAULA R, FERREIRA PM, AFONSO A, et al. (2016) Curcumin Generates Oxidative Stress and Induces Apoptosis in Adult Schistosoma mansoni Worms. PLoS ONE 11(11): e0167135. doi:10.1371/journal. pone.0167135 IF e citações
- PINTO-ALMEIDA A, MENDES T, DE OLIVEIRA RN, CORRÊA SAP, ALLEGRETTI SM, BELO S, TOMÁS A, ANIBAL FF, CARRILHO E and AFONSO A Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and Susceptible Strains Are Different in Presence of Praziquantel. Front. Microbiol. 7:594, 2016.
- PINTO-ALMEIDA, ANTÓNIO; MENDES, TIAGO; ARMADA, ANA; BELO, SILVANA; CARRILHO, EMANUEL; VIVEIROS, MIGUEL; AFONSO, ANA. The Role of Efflux Pumps in Schistosoma mansoni Praziquantel Resistant Phenotype. Plos One, v. 10, p. e0140147, 2015
- AFONSO, ANA; HUNT, P.; ROSARIO, V; CRAVO, P.; CHEESEMAN, S; CUNHA, C. V.; ALVES, A. C. Malaria parasites can develop stable resistance to artemisinin but lack mutations in candidate genes atp6 (encoding the sarcoplasmic and endoplasmic reticulum Ca2+ ATPase), tctp, mdr1, and cg10.. Antimicrobial Agents and Chemotherapy (Print), v. 50, p. 408, 2006.