TY - JOUR
T1 - A Comparative Proteomic Analysis of Praziquantel-Susceptible and Praziquantel-Resistant Schistosoma mansoni Reveals Distinct Response Between Male and Female Animals
AU - Pinto-Almeida, António
AU - Mendes, Tiago M.F.
AU - Ferreira, Pedro
AU - Abecasis, Ana B.
AU - Belo, Silvana
AU - Anibal, Fernanda F.
AU - Allegretti, Silmara M.
AU - Galinaro, Carlos A.
AU - Carrilho, Emanuel
AU - Afonso, Ana
N1 - Funding Information:
We acknowledge the Mass Spectrometry Laboratory at Brazilian Biosciences National Laboratory, CNPEM, Campinas, Brazil for their support with the mass spectrometry analysis. The authors would like to thank Professor Ana Tomás from IBMC and GABBA program (Porto, Portugal), for very helpful suggestions that improved greatly this paper.
Funding Information:
This work was initially supported by Fundação para a Ciência e a Tecnologia de Portugal (FCT) by grant PEst-OE/SAU/UI0074/2014. AP-A was initially funded by Graduate Program in Areas of Basic and Applied Biology (GABBA) from the Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto and FCT (SFRH/BD/51697/2011) meanwhile received the António Coutinho Science Award (11/BI-PD/20) by the Instituto Gulbenkian de Ciência (IGC) of the Fundação Calouste Gulbenkian, and Fundação Familia Merk and Câmara Municipal de Oeiras, and nowadays is funded by the German Federal Ministry of Education and Research (BMBF), the West African Science Service Centre on Climate Change and Adapted Land Use (WASCAL) through WASCAL Graduate Studies Programme in Climate Change and Marine Sciences at the Institute for Enginneering and Marine Sciences, Atlantic Technical University, Cabo Verde. The Brazilian agencies that were involved in this project are Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq Proc. Nrs 400168/2013-8, and 375781/2013-7 that funded AA, and Fundação de Amparo a Pesquisa no Estado de São Paulo – FAPESP Proc. Nrs 2009/54040-8, 2009/16598-7, and 2008/04050-4 that funded infrastructure to EC. Project FAPESP 2014/07331-5 funded infrastructure to FA. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 1742613 and 88882.317690/2019-01, as a fellowship to CG and Finance Code 001 as a fellowship to TM. AA is now being funded by Fundação para a Ciência e Tecnologia (FCT) of Portugal PTDC/CVT-CVT/28798/2017. Fundação para a Ciência e Tecnologia (FCT) of Portugal provided funds to GHTM (UID/Multi/04413/2020) funded PF, ABA, and SB.
Publisher Copyright:
Copyright © 2021 Pinto-Almeida, Mendes, Ferreira, Abecasis, Belo, Anibal, Allegretti, Galinaro, Carrilho and Afonso.
PY - 2021
Y1 - 2021
N2 - Schistosomiasis is a chronic neglected tropical disease saddling millions of people in the world, mainly children living in poor rural areas. Praziquantel (PZQ) is currently the only drug used for the treatment and control of this disease. However, the extensive use of this drug has brought concern about the emergence of PZQ-resistance/tolerance by Schistosoma mansoni. Studies of Schistosoma spp. genome, transcriptome, and proteome are crucial to better understand this situation. In this in vitro study, we compare the proteomes of a S. mansoni variant strain stably resistant to PZQ and isogenic to its fully susceptible parental counterpart, identifying proteins from male and female adult parasites of PZQ-resistant and PZQ-susceptible strains, exposed and not exposed to PZQ. A total of 60 Schistosoma spp. proteins were identified, some of which present or absent in either strain, which may putatively be involved in the PZQ-resistance phenomenon. These proteins were present in adult parasites not exposed to PZQ, but some of them disappeared when these adult parasites were exposed to the drug. Understanding the development of PZQ-resistance in S. mansoni is crucial to prolong the efficacy of the current drug and develop markers for monitoring the potential emergence of drug resistance.
AB - Schistosomiasis is a chronic neglected tropical disease saddling millions of people in the world, mainly children living in poor rural areas. Praziquantel (PZQ) is currently the only drug used for the treatment and control of this disease. However, the extensive use of this drug has brought concern about the emergence of PZQ-resistance/tolerance by Schistosoma mansoni. Studies of Schistosoma spp. genome, transcriptome, and proteome are crucial to better understand this situation. In this in vitro study, we compare the proteomes of a S. mansoni variant strain stably resistant to PZQ and isogenic to its fully susceptible parental counterpart, identifying proteins from male and female adult parasites of PZQ-resistant and PZQ-susceptible strains, exposed and not exposed to PZQ. A total of 60 Schistosoma spp. proteins were identified, some of which present or absent in either strain, which may putatively be involved in the PZQ-resistance phenomenon. These proteins were present in adult parasites not exposed to PZQ, but some of them disappeared when these adult parasites were exposed to the drug. Understanding the development of PZQ-resistance in S. mansoni is crucial to prolong the efficacy of the current drug and develop markers for monitoring the potential emergence of drug resistance.
KW - 2D-electrophoresis
KW - liquid chromatography
KW - mass spectrometry
KW - praziquantel resistance
KW - proteomics
KW - Schistosoma mansoni
UR - http://www.scopus.com/inward/record.url?scp=85132540337&partnerID=8YFLogxK
U2 - 10.3389/fitd.2021.664642
DO - 10.3389/fitd.2021.664642
M3 - Article
AN - SCOPUS:85132540337
VL - 2
JO - Frontiers in Tropical Diseases
JF - Frontiers in Tropical Diseases
M1 - 664642
ER -