Schistosomiasis is one of the most devastating neglected tropical parasitic diseases caused by trematodes of the genusSchistosoma. Praziquantel (PZQ) is today the only drug used in humans and animals for the treatment of schistosomiasis but unfortunately it is poorly effective on larval and juvenile stages of the parasite. Therefore, it is urgent the discovery of new drug targets and compounds. We have recently showed that the anti-anginal drug perhexiline maleate (PHX) is very active on multiple developmental stages ofSchistosoma mansoni in vitro. It is well known that PHX impacts the lipid metabolism in mammals, but the final target on schistosomes still remains unknown. The aim of this study was to evaluate the ability of(1)H nuclear magnetic resonance (NMR) spectroscopy in revealing metabolic perturbations due to PHX treatment ofS.mansoniadult male worms. The effects of PHX were compared with the ones induced by vehicle and gambogic acid, in order to detect different metabolic profiles and specificity of the PHX action. Remarkably a list of metabolites associated to PHX-treatment was identified with enrichment in several connected metabolic pathways including also the Kennedy pathway mediating the glycerophospholipid metabolism. Our study represents the first(1)H-NMR metabolomic approach to characterize the response ofS.mansonito drug treatment. The obtained "metabolic fingerprint" associated to PHX treatment could represent a strategy for displaying cellular metabolic changes for any given drug and to compare compounds targeting similar or distinct biochemical pathways.Author summary Schistosomiasis is a chronic and debilitating neglected tropical parasitic disease caused by the helminthSchistosoma. The control and treatment of the disease rely almost exclusively on praziquantel (PZQ), poorly effective on some developmental stage of the parasite. Identification of novel targets and drugs is required. The aim of this study was to use a(1)H-NMR metabolomic approach to characterize the response ofSchistosoma mansonito perhexiline maleate (PHX), a multi-stage schistosomicidal drug previously investigated by our group. Remarkably we identified a metabolic signature specifically associated to drug-treatment in adult male parasites. This approach could contribute to the identification of novel targets and biochemical pathways implicated in parasite development and survival.

Guidi, A., Petrella, G., Fustaino, V., Saccoccia, F., Lentini, S., Gimmelli, R., et al. (2020). Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by(1)H-NMR spectroscopy. PLOS NEGLECTED TROPICAL DISEASES, 14(10), e0008767 [10.1371/journal.pntd.0008767].

Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by(1)H-NMR spectroscopy

Lentini, S;Cicero, DO
;
2020-10-01

Abstract

Schistosomiasis is one of the most devastating neglected tropical parasitic diseases caused by trematodes of the genusSchistosoma. Praziquantel (PZQ) is today the only drug used in humans and animals for the treatment of schistosomiasis but unfortunately it is poorly effective on larval and juvenile stages of the parasite. Therefore, it is urgent the discovery of new drug targets and compounds. We have recently showed that the anti-anginal drug perhexiline maleate (PHX) is very active on multiple developmental stages ofSchistosoma mansoni in vitro. It is well known that PHX impacts the lipid metabolism in mammals, but the final target on schistosomes still remains unknown. The aim of this study was to evaluate the ability of(1)H nuclear magnetic resonance (NMR) spectroscopy in revealing metabolic perturbations due to PHX treatment ofS.mansoniadult male worms. The effects of PHX were compared with the ones induced by vehicle and gambogic acid, in order to detect different metabolic profiles and specificity of the PHX action. Remarkably a list of metabolites associated to PHX-treatment was identified with enrichment in several connected metabolic pathways including also the Kennedy pathway mediating the glycerophospholipid metabolism. Our study represents the first(1)H-NMR metabolomic approach to characterize the response ofS.mansonito drug treatment. The obtained "metabolic fingerprint" associated to PHX treatment could represent a strategy for displaying cellular metabolic changes for any given drug and to compare compounds targeting similar or distinct biochemical pathways.Author summary Schistosomiasis is a chronic and debilitating neglected tropical parasitic disease caused by the helminthSchistosoma. The control and treatment of the disease rely almost exclusively on praziquantel (PZQ), poorly effective on some developmental stage of the parasite. Identification of novel targets and drugs is required. The aim of this study was to use a(1)H-NMR metabolomic approach to characterize the response ofSchistosoma mansonito perhexiline maleate (PHX), a multi-stage schistosomicidal drug previously investigated by our group. Remarkably we identified a metabolic signature specifically associated to drug-treatment in adult male parasites. This approach could contribute to the identification of novel targets and biochemical pathways implicated in parasite development and survival.
ott-2020
Online ahead of print
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Guidi, A., Petrella, G., Fustaino, V., Saccoccia, F., Lentini, S., Gimmelli, R., et al. (2020). Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by(1)H-NMR spectroscopy. PLOS NEGLECTED TROPICAL DISEASES, 14(10), e0008767 [10.1371/journal.pntd.0008767].
Guidi, A; Petrella, G; Fustaino, V; Saccoccia, F; Lentini, S; Gimmelli, R; Di Pietro, G; Bresciani, A; Cicero, D; Ruberti, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/255703
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