DOI: 10.5281/zenodo.5209299
title: Phenotype, genotype and fitness data related to genetic analysis of praziquantel response in schistosome parasites.

description: These data are related to the study of the Genetic analysis of praziquantel response in schistosome parasites implicates a Transient Receptor Potential channel. Mass treatment with praziquantel (PZQ) monotherapy is the mainstay for schistosomiasis treatment. This drug shows imperfect cure rates in the field and parasites showing reduced PZQ response can be selected in the laboratory, but the extent of resistance in <em>Schistosoma mansoni</em> populations is unknown. We examined the genetic basis of variation in PZQ response in a <em>S. mansoni</em> population (SmLE-PZQ-R) selected with PZQ in the laboratory: 35% of these worms survive high dose (73 µg/mL) PZQ treatment. We used genome wide association to map loci underlying PZQ response. The major chr. 3 peak contains a transient receptor potential (Sm.TRPM_PZQ) channel (Smp_246790), activated by nanomolar concentrations of PZQ. PZQ response shows recessive inheritance and marker-assisted selection of parasites at a single Sm.TRPM_PZQ SNP enriched populations of PZQ-resistant (PZQ-ER) and sensitive (PZQ-ES) parasites showing &gt;377 fold difference in PZQ response. The PZQ-ER parasites survived treatment in rodents better than PZQ-ES. Resistant parasites show 2.25-fold lower expression of Sm.TRPM_PZQ than sensitive parasites. Specific chemical blockers of Sm.TRPM_PZQ enhanced PZQ resistance, while Sm.TRPM_PZQ activators increased sensitivity. A single SNP in Sm.TRPM_PZQ differentiated PZQ-ER and PZQ-ES lines, but mutagenesis showed this was not involved in PZQ response, suggesting linked regulatory changes. We surveyed Sm.TRPM_PZQ sequence variation in 259 parasites from the New and Old World revealing one nonsense mutation that results in a truncated protein with no PZQ-binding site. Our results demonstrate that Sm.TRPM_PZQ underlies variation in PZQ response in <em>S. mansoni</em> and provides an approach for monitoring emerging PZQ-resistance alleles in schistosome elimination programs. This dataset is divided in 3 folders. Each folder has a readme detailing its content. <strong>1-Phenotyping_data</strong> This folder includes the data tables related to the phenotyping of the worms performed during this study. The phenotype measured was the viability of worms following PZQ treatment (i.e., PZQ response). This viability was assessed microscopically or using worm lactate production released in culture media. The data correspond to the following experiments: PZQ response of single adult male worms from SmLE and SmLE-PZQ-R populations to different doses of PZQ. This data was used to determine the PZQ IC50 of each population. Lactate production from single SmLE-PZQ-R adult male worms and correlation with visual observation. This was a proof-of-principle that lactate production can be used to efficiently and unbiasedly phenotype schistosome adult male worms in response to PZQ drug. PZQ response of single SmLE-PZQ-R adult male worms. These worms were then divided in low and high producer in response to PZQ and used to perform a genome-wide association study. PZQ response of single adult male worms from SmLE-PZQ-ER and SmLE-PZQ-ES populations to different doses of PZQ. This data was used to determine the PZQ IC50 of each population. PZQ response of single adult male worms from SmLE-PZQ-ER and SmLE-PZQ-ES populations in presence of Sm.TRPM_PZQ blocker (MB2) and activator (MV1) with and without PZQ drug. In vivo PZQ response of schistosome worms from SmLE-PZQ-ER and SmLE-PZQ-ES populations. <strong>2-Genotyping_data</strong> This folder includes the data tables related to the genotyping of the worms performed during this study. Worms were genotyping using PCR-RFLP (genotyping of single nucleotide polymorphisms (SNPs) on chr2 and chr3 QTLs) or using qPCR (genotyping of a copy number variation (CNV) on chr3 QTL). The data correspond to the following experiment: Association between PZQ response of single adult male worms from SmLE-PZQ-R population and their respective genotype on chromosome 2 (SNP) and chromosome 3 (SNP and CNV) loci. <strong>3-Fitness_data</strong> This folder includes the data tables related to the fitness of the parasite populations. We collected data regarding: The number of surviving and infected snails after exposure to SmLE-PZQ-ER or SmLE-PZQ-ES miracidia. The number of adult worms recovered from golden Syrian female hamsters exposed to SmLE-PZQ-ER or SmLE-PZQ-ES cercariae. All the data were collected during 12 generations of parasites and are used to evaluate a potential impact of PZQ resistance on the parasite fitness.