Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel

Abstract

Background Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is the drug of choice for the treatment of Mekong schistosomiasis. However, the molecular mechanisms of PZQ action remain unclear, and Schistosoma PZQ resistance has been reported occasionally. Through this research, we aimed to use a metabolomic approach to identify the potentially altered metabolic pathways in S. mekongi associated with PZQ treatment. Methodology/Principal findings Adult stage S. mekongi were treated with 0, 20, 40, or 100 μg/mL PZQ in vitro. After an hour of exposure to PZQ, schistosome metabolites were extracted and studied with mass spectrometry. The metabolomic data for the treatment groups were analyzed with the XCMS online platform and compared with data for the no treatment group. After low, medium (IC50), and high doses of PZQ, we found changes in 1,007 metabolites, of which phosphatidylserine and anandamide were the major differential metabolites by multivariate and pairwise analysis. In the pathway analysis, arachidonic acid metabolism was found to be altered following PZQ treatment, indicating that this pathway may be affected by the drug and potentially considered as a novel target for anti-schistosomiasis drug development. Conclusions/Significance Our findings suggest that arachidonic acid metabolism is a possible target in the parasiticidal effects of PZQ against S. mekongi. Identifying potential targets of the effective drug PZQ provides an interesting viewpoint for the discovery and development of new agents that could enhance the prevention and treatment of schistosomiasis.

Harnessing Schistosoma-associated metabolite changes in the human host to identify biomarkers of infection and morbidity: Where are we and what should we do next?

“…Moreover, the use of cohorts undergoing treatment with praziquantel would help exclude non-robust candidate metabolites and uniquely reveal reliable metabolites that evolve in a timely manner with the host’s infection and disease status during schistosomiasis. Such attempts have already been undertaken in preclinical [ 79 ] as well as clinical settings [ 42 ], validating the power of such an approach of longitudinal follow up with treatment while also providing an exploitable list of candidate metabolite biomarkers during schistosomiasis. A consequent expectation would be the identification of metabolite biomarkers of infection acquisition or disease progression in individuals initially uninfected and disease-free upon long-term follow up in endemic areas.…”

Anti-fibrotic Effect of Oral Versus Intraperitoneal Administration of Gold Nanoparticles in Hepatic Schistosoma mansoni-Infected Mice

“…Schistosomiasis is a parasitic disease caused by blood-dwelling trematode worms of Schistosoma [ 1 ]. There are six major human-infecting species, with Schistosoma mansoni ( S. mansoni ), S. haematobium , and S. japonicum accounting for the preponderance of human disease burdens [ 2 ].…”

“…Fig.1Serum albumin levels in the in vivo assay 1. Non-significant differences from IT-PZQ in comparison to InT group; 2 Significant differences from IT-AuNPs-Peritoneal in comparison to InT group; 3 Significant differences from IT-AuNPs-Oral in comparison to InT group…”

Metagenomic Analysis Reveals Variations in Gut Microbiomes of the Schistosoma mansoni-Transmitting Snails Biomphalaria straminea and Biomphalaria glabrata

“…Endemic in 77 countries in tropical and subtropical regions, schistosomiasis poses a threat to approximately one-eighth of the global population. The disease is caused by different species of Schistosoma, including Schistosoma mansoni [3][4][5], S. japonicum [6][7][8][9], S. haematobium [10,11], S. intercalatum [12] and S. Mekongi [13][14][15], of which S. mansoni is one of the most widespread species [2,3]. Biomphalaria snails such as Biomphalaria straminea and B. glabrata are important intermediate hosts of S. mansoni.…”