Transcriptional phenotype of the anti-parasitic benzodiazepine meclonazepam on the blood fluke Schistosoma mansoni
Year: 2025
Type: article
Abstract: There are limited control measures for the disease schistosomiasis, despite the fact that infection with parasitic blood flukes affects hundreds of millions of people worldwide. The current treatment, praziquantel, has been in use since the 1980's and there is a concern that drug resistance may emerge with continued monotherapy. Given the need for additional antischistosomal drugs, we have re-visited an old lead, meclonazepam. In comparison to praziquantel, there has been relatively little work on its antiparasitic mechanism. Recent findings indicate that praziquantel and meclonazepam act through distinct receptors, making benzodiazepines a promising chemical series for further exploration. Previous work has profiled the transcriptional changes evoked by praziquantel treatment. Here, we examine in detail schistosome phenotypes evoked by in vitro and in vivo meclonazepam treatment. These data confirm that meclonazepam causes extensive tegument damage and directly kills parasites, as measured by pro-apoptotic caspase activation. In vivo meclonazepam exposure results in differential expression of many genes that are divergent in parasitic flatworms, as well as several gene products implicated in blood feeding and regulation of hemostasis in other parasites. Many of these transcripts are also differentially expressed with praziquantel exposure, which may reflect a common schistosome response to the two drugs. However, despite these similarities in drug response, praziquantel-resistant parasites retain susceptibility to meclonazepam's schistocidal effects. These data provide new insight into the mechanism of antischistosomal benzodiazepines, resolving similarities and differences with the current frontline therapy, praziquantel.
Source: PLoS neglected tropical diseases
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,670
Awards: G1073451793, G1173815590, G159247434, G2169778925, G2197417141, G2518373647, G2870346016, G2903083770, Genetic Basis of Praziquantel Resistance, G305836430, G4121272638, G6238307464, G6253890364, G6855171693, MOLECULAR AND BIOCHEMICAL GENETICS LABORATORY RENOVATION, Discovery of new molecular phenotypes for anti-schistosomal drug screening, G858414853, G9000039734, G9000131645, G9000140201, G9000210540, The Southwest National Primate Research Center, Genomic consequences of schistosome hybridization
OpenAlex ID: W4409257269