Biology subjects

Sanya, R.

Publications and source records attributed to Sanya, R..

3 recordsLinked to original sources

bioRxiv2024

Extensive transmission and variation in a functional receptor for praziquantel resistance in endemic Schistosoma mansoni

Mass-drug administration (MDA) of human populations using praziquantel monotherapy has become the primary strategy for controlling and potentially eliminating the major neglected tropical disease schistosomiasis. To understand how long-term MDA impacts schistosome populations, we analysed whole-genome sequence data of 570 Schistosoma mansoni samples (and the closely related outgroup species, S. rodhaini) from eight countries incorporating both publicly-available sequence data and new parasite material. This revealed broad-scale genetic structure across countries but with extensive transmission over hundreds of kilometres. We characterised variation across the transient receptor potential melastatin ion channel, TRPMPZQ, a target of praziquantel, which has recently been found to influence praziquantel susceptibility. Functional profiling of TRPMPZQ variants found in endemic populations identified four mutations that reduced channel sensitivity to praziquantel, indicating standing variation for resistance. Analysis of parasite infrapopulations sampled from individuals pre- and post-treatment identified instances of treatment failure, further indicative of potential praziquantel resistance. As schistosomiasis is targeted for elimination as a public health problem by 2030 in all currently endemic countries, and even interruption of transmission in selected African regions, we provide an in-depth genomic characterisation of endemic populations and an approach to identify emerging praziquantel resistance alleles. One Sentence SummaryPopulation genomics and functional genetics of praziquantel resistance in Schistosoma mansoni

genomics↗

bioRxiv2023

Assessment of genetic diversity patterns of different serotypes of dengue virus, prevalent in patients from Kerala, India: a strain specific mutation study and its relevance to pathogenesis

The mutations are the key mechanisms responsible for virus survival and its fitness in the host. This process of mutation is implicated in the development of pathogenesis of the dengue viral disease. We report that, all the four serotypes were found to be circulating in Kerala sate of India. Serotypes 1 and 3 were the predominant type (33.3 %) compared to others. The prevalence of co-infection of serotype 1 and 4 was the highest percentage (11.1 %) compared to serotype 2 and serotype 3 (5.5 %). We further highlighted the immunopathological mechanisms of antibody neutralization, CD4+ T cell response and antibody dependent enhancements (ADE) for the possible cause of disease severity in coinfections. Serotype-1 does not show much variations from the previously reported strains from various regions of India. However, serotype-2 showed variations in the sequences from the other strains of serotype-2 previously reported from various regions of India and formed a distinct clade in the genotype-4. Serotype-3 and serotype-4 showed similarity with previously reported strains from India. Moreover, serotype-1 was grouping in genotype-5. Importantly, the serotype-2 grouped with genoptype-4 but exist separately. Serotype-3 was found to be grouped with the genotype-3. The serotype-4 show the very much similarities from the genotype-1 and shows little difference from the previously reported strains from India. Further, mutation in DENV-3 sequences, at position 235 (C to T) and 322 (G to T) shows an important phenomenon which might be adopted by the virus to survive. As severe dengue is linked with the serotype-2, the genetic variations in this serotype points towards the much specific strategy to be adopted in near future to manage the severe dengue disease. In conclusion, we can say that, genetic diversity in the CprM region is present in the different serotypes circulating in the patients from Kerala India and this information may help in the management of dengue viral disease.

immunology↗

bioRxiv2022

Genome-wide analysis of Schistosoma mansoni reveals population structure and praziquantel drug selection pressure within Ugandan hot-spot communities

Populations within schistosomiasis control areas, especially those in Africa, are recommended to receive regular mass drug administration (MDA) with praziquantel (PZQ) as the main strategy for controlling the disease. The impact of PZQ treatment on schistosome genetics remains poorly understood, and is limited by a lack of high-resolution genetic data on the population structure of parasites within these control areas. We generated whole-genome sequence data from 174 individual miracidia collected from both children and adults from fishing communities on islands in Lake Victoria in Uganda that had received either annual or quarterly MDA with PZQ over four years, including samples collected immediately before and four weeks after treatment. Genome variation within and between samples was characterised and we investigated genomic signatures of natural selection acting on these populations that could be due to PZQ treatment. The parasite population on these islands was more diverse than found in nearby villages on the lake shore. We saw little or no genetic differentiation between villages, or between the groups of villages with different treatment intensity, but slightly higher genetic diversity within the pre-treatment compared to post-treatment parasite populations. We identified classes of genes significantly enriched within regions of the genome with evidence of recent positive selection among post-treatment and intensively treated parasite populations. The differential selection observed in post-treatment and pre-treatment parasite populations could be linked to any reduced susceptibility of parasites to praziquantel treatment. Author summarySchistosomiasis is caused by parasitic helminths of the genus Schistosoma. Schistosoma mansoni is the primary cause of intestinal schistosomiasis, a devastating and widespread parasitic infection that causes morbidity, death and socio-economic impact on endemic communities across the world and especially sub-Saharan Africa. Using whole-genome sequencing, we were able to elucidate the parasite population within Lake Victoria island fishing communities in Uganda which are among the major hotspots for schistosomiasis. We further assessed genetic markers that might be linked to recent observations concerning reduced susceptibility to praziquantel, the major drug used in the treatment of this disease. Whole-genome data on the population genetics of S. mansoni in an African setting will provide a strong basis for future functional genomics or transcriptomic studies that will be key to identifying drug targets, improving existing drugs or developing new therapeutic interventions.

genomics↗