DEPARTMENT FOR SCIENCE, INNOVATION AND TECHNOLOGY

Characterizing Molecular Adaptations and Drug Resistance in Leishmania spp. in Thailand: An Integrative Omics Approach to Combat Leishmaniasis

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Description

Leishmaniasis, a neglected tropical disease caused by protozoan parasites of the genus Leishmania, presents a growing global health concern. In Thailand, the emergence of leishmaniasis, potentially transmitted by atypical vectors, poses a significant threat to immunocompromised individuals, particularly those co-infected with HIV. In addition, climate change is a potential increase in disease prevalence by altering insect vector distribution and population dynamics. Amphotericin B remains the primary treatment for leishmaniasis in Thailand, and Leishmania species of the subgenus Mundinia (L. orientalis and L. martiniquensis) exhibit relative insensitivity to this drug. Preliminary experiments displayed initial genomic and transcriptomic alteration after short-term treatments of L. orientalis with amphotericin B. This resistance is concerning as it may be associated with increased parasite fitness and potentially higher virulence. Addressing these critical issues necessitates a deep understanding of drug resistance and parasite adaptation mechanisms for the development of effective strategies for treatments. This research project leverages a pre-existing collaboration between researchers from the University of Glasgow (UK) and Kasetsart University (Thailand), which previously explored genomic structures of L. orientalis and L. martiniquensis strains in Thailand. The project aims to characterize molecular changes occurring during Amphotericin B selection in L. orientalis and L. martiniquensis using integrative omics technologies, parasite phenotyping and advanced computational analysis. We will investigate both innate and in vitro-acquired resistance using polyomic approaches, including bulk and single-cell sequencing and transcriptomics, proteomics, metabolomics and lipidomics, in parallel with assessing important phenotypes such as drug sensitivity and infectivity to macrophages. We will elucidate mechanisms of resistance and to identify markers that can predict Amphotericin-treatment failure. The collaborative research between the UK and Thailand teams will accelerate understanding these newly reported Leishmania parasites and benefit the control of leishmaniasis in Thailand and beyond. Bilateral knowledge exchange between Thailand and UK will be a key outcome of our project, leading to capacity building in Thailand and the establishment of critical collaboration between parasitologists working in the UK and scientists in Thailand, a country with an developing science base and an emerging problem with leishmaniasis.

Objectives

Leishmaniasis, a neglected tropical disease caused by protozoan parasites of the genus Leishmania, presents a growing global health concern. In Thailand, the emergence of leishmaniasis, potentially transmitted by atypical vectors, poses a significant threat to immunocompromised individuals, particularly those co-infected with HIV. In addition, climate change is a potential increase in disease prevalence by altering insect vector distribution and population dynamics. Amphotericin B remains the primary treatment for leishmaniasis in Thailand, and Leishmania species of the subgenus Mundinia (L. orientalis and L. martiniquensis) exhibit relative insensitivity to this drug. Preliminary experiments displayed initial genomic and transcriptomic alteration after short-term treatments of L. orientalis with amphotericin B. This resistance is concerning as it may be associated with increased parasite fitness and potentially higher virulence. Addressing these critical issues necessitates a deep understanding of drug resistance and parasite adaptation mechanisms for the development of effective strategies for treatments. This research project leverages a pre-existing collaboration between researchers from the University of Glasgow (UK) and Kasetsart University (Thailand), which previously explored genomic structures of L. orientalis and L. martiniquensis strains in Thailand. The project aims to characterize molecular changes occurring during Amphotericin B selection in L. orientalis and L. martiniquensis using integrative omics technologies, parasite phenotyping and advanced computational analysis. We will investigate both innate and in vitro-acquired resistance using polyomic approaches, including bulk and single-cell sequencing and transcriptomics, proteomics, metabolomics and lipidomics, in parallel with assessing important phenotypes such as drug sensitivity and infectivity to macrophages. We will elucidate mechanisms of resistance and to identify markers that can predict Amphotericin-treatment failure. The collaborative research between the UK and Thailand teams will accelerate understanding these newly reported Leishmania parasites and benefit the control of leishmaniasis in Thailand and beyond. Bilateral knowledge exchange between Thailand and UK will be a key outcome of our project, leading to capacity building in Thailand and the establishment of critical collaboration between parasitologists working in the UK and scientists in Thailand, a country with an developing science base and an emerging problem with leishmaniasis.

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Location

The country, countries or regions that benefit from this Programme.

Thailand

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