Revisiting Schistosoma mansoni Micro-Exon Gene (MEG) Protein Family: A Tour into Conserved Motifs and Annotation

Nedvědová, Štěpánka; De Stefano, Davide; Walker, Olivier; Hologne, Maggy; Miele, Adriana Erica

doi:10.3390/biom13091275

Cited by 2 publications

References 42 publications

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Transcriptional phenotype of the anti-parasitic benzodiazepine meclonazepam on the blood flukeSchistosoma mansoni

Henthorn,

McCusker,

Clec’h

et al. 2024

Preprint

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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.

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Transcriptional phenotype of the anti-parasitic benzodiazepine meclonazepam on the blood flukeSchistosoma mansoni

Henthorn,

McCusker,

Clec’h

et al. 2024

Preprint

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Apicomplexan Pore-Forming Toxins

Carruthers

2024

Annual Review of Microbiology

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Pore-forming toxins (PFTs) are released by one cell to directly inflict damage on another cell. Hosts use PFTs, including members of the membrane attack complex/perforin protein family, to fight bacterial infections and cancer, while bacteria and parasites deploy PFTs to promote infection. Apicomplexan parasites secrete perforin-like proteins as PFTs to egress from infected cells and traverse tissue barriers. Other protozoa, along with helminth parasites, utilize saposin-like PFTs prospectively for nutrient acquisition during infection. This review discusses seminal and more recent advances in understanding how parasite PFTs promote infection and describes how they are regulated and fulfill their roles without causing parasite self-harm. Although exciting progress has been made in defining mechanisms of pore formation by PFTs, many open questions remain to be addressed to gain additional key insights into these remarkable determinants of parasitic infections.

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Revisiting Schistosoma mansoni Micro-Exon Gene (MEG) Protein Family: A Tour into Conserved Motifs and Annotation

Cited by 2 publications

References 42 publications

Transcriptional phenotype of the anti-parasitic benzodiazepine meclonazepam on the blood flukeSchistosoma mansoni

Transcriptional phenotype of the anti-parasitic benzodiazepine meclonazepam on the blood flukeSchistosoma mansoni

Apicomplexan Pore-Forming Toxins

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