Schistosomes are human parasitic blood fluke that infect over 200 million people worldwide (South-America, Caribbean, Africa, Middle-east, Asia), causing schistosomiasis disease. This chronic and debilitating tropical disease is the first helminthic disease in term of morbidity and mortality (200,000 deaths each year, mainly teenagers). Schistosomiasis is a waterborne disease: infected freshwater snails release larvae (cercariae) which infect humans during their water related activities.
No efficient vaccine is available and only one drug – praziquantel – is currently used to treat patients but drug resistance is on the rise. Moreover, this drug is efficient against adult worms but not immature worms that develop in the human body. Therefore innovative approaches are needed to identify new drug targets, understand drug resistance at the genetic and molecular level, develop molecular surveillance approaches to detect drug resistant parasites in the field, and decipher the complex interactions between the different hosts (snails, humans) and the schistosome parasite.
Inside the Lab
Working with Dr. Tim Anderson, Dr. Le Clec’h is focusing on genetics of the schistosome parasites, schistosome drug resistance and also the microbiome of snail host.
Identification of drug resistance genes and design of new drugs are of major importance for this disease since only one drug – praziquantel – is available. Current mass treatment campaigns (2016-2021) aim to distribute 250 million praziquantel tablets per year, constituting a 10-fold increase in tablet distribution, intensifying selection for praziquantel resistance in schistosome populations. Identifying praziquantel resistance gene is fundamental to then be able to identify genetic markers linked to resistance, develop molecular surveillance approaches to detect drug resistant parasites in the field and elucidate the praziquantel mechanism(s) of action that remains unknown.
In parallel with drug resistance, Dr. Le Clec’h is studying the genetic basis of a biomedically important trait of this parasite: the production of cercaria larvae (infectious stage for humans). These larvae are shed from infected snails and the number of larvae produced is directly associated with its transmission success. This number varies significantly within and between different parasite populations and selection experiments demonstrate that this variation has a strong genetic basis. Understanding the fundamental biology of the parasites may also open new avenues for drug targets.
The freshwater snail vector is a critical part of the schistosome lifecycle. This snail harbors a diverse microbiome – the microorganism community that inhabits on or within animal body – which may represent a critical, but unexplored intermediary in the snail-schistosome interaction. By studying the microbiome of the snail, we could discover new mechanisms to control schistosome through its vector.
Main Technologies and Methods Used
- Library preparation for high-throughput sequencing (exome capture, RNA-seq, MiSeq)
- PCR / RT-PCR / qPCR / PCR-RFLP
- Sanger sequencing
- Whole genome amplification
- Rodents perfusion / worm and egg collection
- Long term worms in vitro culture
- Drug treatment assays
- Metabolism assay to assess worm survival after drug treatment
- Snail rearing and infection
- Quantitative trait loci (QTL) analysis
- Survival analysis
- Phylogenetic analysis
- Microbiome analysis
- Scripting (bash, R, LaTeX)