Publications by authors named "Malgorzata Anna Domagalska"

We sequenced Leishmania donovani genomes in blood samples collected in emerging foci of visceral leishmaniasis in western Nepal. We detected lineages very different from the preelimination main parasite population, including a new lineage and a rare one previously reported in eastern Nepal. Our findings underscore the need for genomic surveillance.

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Introduction: Resistance against anti- drugs (DR) has been studied for years, giving important insights into long-term adaptations of these parasites to drugs, through genetic modifications. However, microorganisms can also survive lethal drug exposure by entering into temporary quiescence, a phenomenon called drug tolerance (DT), which is rather unexplored in .

Methods: We studied a panel of nine strains highly susceptible to potassium antimonyl tartrate (PAT), exposed promastigotes to lethal PAT pressure, and compared several cellular and molecular parameters distinguishing DT from DR.

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is a zoonotic Old World parasite transmitted by Phlebotomine sand flies and causing cutaneous leishmaniasis in Ethiopia and Kenya. Despite a range of clinical manifestations and a high prevalence of treatment failure, is one of the most neglected species of the genus in terms of scientific attention. Here, we explored the genome diversity of by analyzing the genomes of twenty isolates from Ethiopia.

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Treatment failure (TF) jeopardizes the management of parasitic diseases, including leishmaniasis. From the parasite's point of view, drug resistance (DR) is generally considered as central to TF. However, the link between TF and DR, as measured by in vitro drug susceptibility assays, is unclear, some studies revealing an association between treatment outcome and drug susceptibility, others not.

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Microorganisms can adopt a quiescent physiological condition which acts as a survival strategy under unfavorable conditions. Quiescent cells are characterized by slow or non-proliferation and a deep downregulation of processes related to biosynthesis. Although quiescence has been described mostly in bacteria, this survival skill is widespread, including in eukaryotic microorganisms.

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Article Synopsis
  • The study emphasizes the need for prospective drug resistance (DR) investigations in neglected tropical diseases (NTDs), particularly using Leishmania donovani and the drug TCMDC-143345 as examples.
  • Researchers observed that it took longer for L. donovani to develop resistance to TCMDC-143345 compared to existing drugs, indicating a unique resistance mechanism without cross-resistance.
  • Genetic analysis revealed two mutations in the LdoDLP1 protein that contribute to this resistance, affecting mitochondrial properties and suggesting a specific role of LdoDLP1 in the adaptation of L. donovani to the drug.
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Cytosine C5 methylation is an important epigenetic control mechanism in a wide array of eukaryotic organisms and generally carried out by proteins of the C-5 DNA methyltransferase family (DNMTs). In several protozoans, the status of this mechanism remains elusive, such as in , the causative agent of the disease leishmaniasis in humans and a wide array of vertebrate animals. In this work, we showed that the genome contains a C-5 DNA methyltransferase () from the subfamily, whose function is still unclear, and verified its expression at the RNA level.

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Elimination programs targeting TriTryp diseases (Leishmaniasis, Chagas' disease, human African trypanosomiasis) significantly reduced the number of cases. Continued surveillance is crucial to sustain this progress, but parasite molecular surveillance by genotyping is currently lacking. We explain here which epidemiological questions of public health and clinical relevance could be answered by means of molecular surveillance.

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Visceral leishmaniasis (VL), the most severe form of the disease, is caused by Leishmania donovani in the Indian sub-continent (ISC). Whole genome sequencing studies revealed that two parasite populations exist in the ISC: a main population named the Core Group (CG) found mostly in the lowlands, and a new, genetically different subpopulation called ISC1. Parasites belonging to the CG were shown to be responsible for the recent epidemics, while the ISC1 variant was originally identified in hilly districts of Nepal and was later on increasingly found in the lowlands.

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