Biology subjects

Kincaid-Smith, J.

Publications and source records attributed to Kincaid-Smith, J..

5 recordsLinked to original sources

bioRxiv2025

TRPtracker: a community database for monitoring praziquantel sensitivity at TRPMPZQ variants

The anthelmintic praziquantel (PZQ) has been used for decades as the clinical therapy for schistosomiasis, and remains the only available drug. As a cheap and effective drug therapy for all human disease-causing Schistosoma species, usage of PZQ underpins mass drug administration strategies aimed at eliminating schistosomiasis as a public health problem by 2030. Concern over the potential emergence of resistance to PZQ is therefore warranted, as it would constitute a major threat to this approach. In terms of molecular adaptations conferring PZQ resistance, variation in the sequence and/or expression of the drug target is an obvious mechanism and should be a priority for surveillance efforts. The target of PZQ is a transient receptor potential ion channel, TRPMPZQ, which is established as a locus that regulates schistosome sensitivity to PZQ. Here, we describe the establishment of a community resource, TRPtracker, which coalesces data on TRPMPZQ natural variants together with measurements of individual variant sensitivity to PZQ. A compendium of laboratory-generated mutants in TRPMPZQ is also compiled in TRPtracker to map regions within TRPMPZQ critical for PZQ sensitivity. Aggregation of data from multiple research groups into TRPtracker permits rapid community-wide exchange of data, cataloguing which TRPMPZQ variants have been functionally profiled, where geographically these variants have been found, their frequency within populations and their potential impact on PZQ sensitivity.

microbiology↗

bioRxiv2024

Transcriptomic plasticity in hybrid schistosomes can contribute to their zoonotic potential

Hybrids between Schistosoma haematobium and S. bovis are linked to both human and animal infections, highlighting the complex interspecies interactions that contribute to the spread of schistosomiasis. Additionally, S. bovis can infect multiple ruminant hosts, facilitating cross- species transmission and increasing the risk of zoonotic outbreaks. In this study, we investigated transcriptomic plasticity as a potential mechanism enabling hybrid schistosomes to adapt to alternative definitive hosts. We focused on two contexts: 1) introgressed S. haematobium x S. bovis hybrids, which demonstrated higher virulence in sheep compared to parental S. bovis, and 2) S. bovis infecting different host species. Our analysis uncovered 366 differentially expressed genes (DEGs), representing 4% of the total protein-coding genes, between introgressed hybrids and parental S. bovis in sheep. We also identified transcriptomic changes in S. bovis across different mammalian hosts (hamster and sheep), with around 30% of the total genes differentially expressed, demonstrating that S. bovis parasites display a high transcriptomic plasticity, allowing them to infect different definitive hosts. Shared enriched biological processes during introgression and host change include nuclear-transcribed mRNA catabolic processes, inner mitochondrial membrane organization, microtubule-based movement, response to endoplasmic reticulum stress, and sensory perception. These findings suggest that transcriptomic plasticity in S. bovis and hybrid worms enhance their ability to adapt and infect diverse host species, potentially increasing their zoonotic potential. This raises concerns for schistosomiasis epidemiology, as this plasticity could expand the parasites transmission capacity and complicate control efforts.

evolutionary biology↗

bioRxiv2023

Schistosoma haematobium and Schistosoma bovis first generation hybrids undergo large gene expressions remodeling consistent with species compatibility

When two species hybridize, the two parental genomes are brought together and some alleles might interact for the first time. To the date, the extent of the transcriptomic changes in first hybrid generations, along with their functional outcome constitute an important knowledge gap especially in non-model organisms. Here we explored the molecular and functional outcomes of hybridization in first-generation hybrid between the blood fluke parasites S. haematobium and S. bovis. To this aim we fist assembled a hybrid reference transcriptome allowing us to measure gene expression in both parental species and hybrids to further described and quantified the profiles of gene expression encountered in hybrids. We identified large-scale gene expression remodeling since up to 55% of genes were differentially expressed in hybrids compared to at least one of the parental species. We further showed that intermediate level of expression in hybrids compared to parental species was the most prevalent expression profile (38% of genes) in agreement with S. haematobium x S. bovis high genomic compatibility and limited divergence. Also, among the differentially expressed genes of each of the identified profiles (intermediate, under-, over-expressed, or matching the expression of one of the parental species), only a few biological processes were found enriched without patterns being consistent through crosses and sexes. Our findings suggest that hybrid heterosis could be due to change in expression of a large portion of random genes which affect various biological processes. Author SummaryWhen two species manage to produce a viable offspring, due to different parental genetic material, new allelic interactions might arise. We do not know much about how genes are expressed in such hybrids compared to their parental species and especially for non-model species. Here we gene expressions in first generation hybrids of two blood flukes parasites Schistosoma haematobium and S. bovis. We quantified and categorized gene differentially expressed in first generation hybrids. We showed that more than half the genes of the hybrids were differentially expressed compared to at least one of their parental species, hence showing major gene expression remodeling occurring during hybridization. However, the most common hybrid expression pattern was intermediate level of expression compared to parental species and various but no specific biological processes were associated with hybrids differentially expressed genes. We hypothesized that because S. haematobium and S. bovis remain very compatible, when hybridizing many non-specific genes can have their expression level remodeled hence impacting the overall molecular machinery of the offspring while still sustaining highly operational hybrids.

evolutionary biology↗

bioRxiv2022

MALDI-TOF : A new tool for the identification of Schistosoma cercariae and detection of hybrids

Schistosomiasis is a neglected water-born parasitic disease caused by Schistosoma affecting more than 200 million people. Introgressive hybridization is common among these parasites and raises issues concerning their zoonotic transmission. Morphological identification of Schistosoma cercariae is difficult and does not permit hybrids detection. Our objective was to assess the performance of MALDI-TOF for the specific identification of cercariae in human and non-human Schistosoma and for the detection of hybridization between S. bovis and S. haematobium Spectra were collected from laboratory reared molluscs infested with strains of S. haematobium, S. mansoni, S. bovis, S. rodhaini and S. bovis x S. haematobium natural (Corsican hybrid) and artificial hybrids. Cluster analysis showed a clear separation between S. haematobium, S. bovis, S. mansoni and S. rodhaini. Corsican hybrids are classified with those of the parental strain of S. haematobium whereas other hybrids formed a distinct cluster. In blind test analysis the developed MALDI-TOF spectral database permits identification of Schistosoma cercariae with high accuracy (94%) and good specificity (S. bovis: 99.59%, S. haematobium 99.56%, S. mansoni and S. rodhaini: 100%). Most misidentifications were between S. haematobium and the Corsican hybrids. The use of machine learning permits to improve the discrimination between these last two taxa, with accuracy, F1 score and Sensitivity/Specificity > 97%. In multivariate analysis the factors associated with obtaining a valid identification score (> 1.7) were absence of ethanol preservation (p < 0.001) and a number of 2-3 cercariae deposited per well (p < 0.001). Also spectra acquired from S. mansoni cercariae are more likely to obtain a valid identification score than those acquired from S. haematobium (p<0.001). MALDI-TOF is a reliable technique for high-throughput identification of Schistosoma cercariae of medical and veterinary importance and could be useful for field survey in endemic areas. Author SummarySchistosomoses are neglected tropical diseases, affecting approximately 200 million people worldwide. They are transmitted during contact with water contaminated with the infesting stage of the parasite (the cercaria stage). Species-level recognition of cercariae present in water has important implications for field campaigns aimed at eradicating schistosomiasis. In addition, Schistosomes are able to hybridize between different species. Identification of Schistosomes cercariae on microscopy is difficult because of their similarity, and it does not allow hybrids to be distinguished. Molecular biology techniques allow a reliable diagnosis but are expensive. MALDI-TOF is a recent technique that permits an inexpensive identification of micro-organisms in a few minutes. In this paper, we evaluate MALDI-TOF identification of Schistosomes cercariae. We have implemented a database of MALDI-TOF cercariae spectra obtained from parental strains and hybrids of species of medical or veterinary interest, allowing reliable identification with an accuracy of 94%. The identification errors mainly come from confusion between the natural Corsican hybrid (S. haematobium x S. bovis) and S. haematobium. The use of machine learning algorithms permits to obtain an accuracy of more than 97% in the recognition of these two parasites. In conclusion, MALDI-TOF is a promising tool for the identification of Schistosome cercariae.

microbiology↗

bioRxiv2018

Whole genome sequencing and morphological analysis of the human-infecting schistosome emerging in Europe reveals a complex admixture between Schistosoma haematobium and Schistosoma bovis parasites.

Schistosomes cause schistosomiasis, the worlds second most important parasitic disease after malaria. A peculiar feature of schistosomes is their ability to produce viable and fertile hybrids. Originally only present in the tropics, schistosomiasis is now also endemic in Europe. Based on two genetic markers the European species had been identified as a hybrid between the ruminant-infective Schistosoma bovis and the human-infective Schistosoma haematobium.\n\nHere we describe for the first time the genomic composition of the European schistosome hybrid (77% of S. haematobium and 23% of S. bovis origins), its morphometric parameters and its compatibility with the European vector snail and intermediate host Compatibility is a key parameter for the parasites life cycle progression. We also show that egg morphology (a classical diagnostic parameter) does not allow for differential diagnosis while genetic tests do so. Additionally, we performed genome assembly improvement and annotation of S. bovis, the parental species for which no satisfactory genome assembly was available.\n\nFor the first time since the discovery of hybrid schistosomes, these results reveal at the whole genomic level a complex admixture of parental genomes highlighting (i) the high permeability of schistosomes to other species alleles, and (ii) the importance of hybrid formation for pushing species boundaries not only conceptionally but also geographically.

genomics↗