Proteomic analysis reveals differential responses to praziquantel in two Schistosoma mansoni strains with distinct phenotypes.

Different Schistosoma mansoni strains may exhibit distinct phenotypes, which can influence parasite distribution, treatment outcomes, and control strategies. In this study, we conducted a label-free quantitative proteomic analysis to compare two strains of S. mansoni, Belo Horizonte (SmBH) and Sergipe (SmSE), which differ in phenotypic traits and susceptibility to praziquantel (PZQ). BALB/c mice were infected and treated with a sub-curative dose of PZQ (50 mg/kg) 45 days post-infection. Male and female worms were recovered 15 days after treatment, and pooled samples were processed for trypsin digestion and mass spectrometry. Over 1000 proteins were identified. No significant differences were observed in protein expression between untreated females of the two strains. In untreated males, 16 proteins showed differential expression: 11 upregulated in SmBH, mostly related to metabolic and energy production pathways, and 5 upregulated in SmSE. PZQ exposure did not significantly alter protein expression in SmBH worms. In contrast, SmSE males showed 74 differentially expressed proteins post-treatment, with 58 upregulated, including proteins with antioxidant and antiapoptotic functions commonly associated with drug resistance. SmSE females showed upregulation of three proteins after treatment, mostly related to cytoskeletal and muscular structure, suggesting less PZQ-induced damage. These results suggest that SmSE exhibits adaptive proteomic responses to PZQ-induced oxidative stress, which may contribute to its increased survival after treatment. Our findings provide molecular insight into strain-specific responses to PZQ and highlight potential mechanisms underlying reduced drug susceptibility in S. mansoni.