A Leishmania parasite in Thailand is becoming less responsive to the only drug available to treat it, and researchers want to know why. This matters because leishmaniasis, a parasitic disease spread by sandflies, is emerging in Thailand—particularly among people with HIV—and the local *Leishmania* species already show relative insensitivity to amphotericin B, the primary treatment. Preliminary experiments found that short-term drug exposure triggers genomic and transcriptomic changes in the parasite, raising the possibility that resistance could worsen and make infections harder to treat. The project will map the molecular changes that occur when *L. orientalis* and *L. martiniquensis* develop drug resistance, using a suite of omics technologies—genomics, transcriptomics, proteomics, metabolomics, and lipidomics—alongside tests of drug sensitivity and infectivity to human immune cells. If the team identifies markers that predict treatment failure, clinicians could one day test for resistance before choosing a therapy, improving outcomes for immunocompromised patients. The collaboration also builds research capacity in Thailand, where leishmaniasis is a growing but understudied problem.
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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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