Publications by authors named "Gabriel Negreira"
Article Synopsis
- Aneuploidy, often seen as harmful, can help some microorganisms adapt to environmental stress, such as in the case of Leishmania, a protozoan parasite.
- The study utilized advanced techniques like single-cell genomics to show that under antimony pressure, existing genetic variations (karyotypes) are selected, plus rapid changes in chromosome numbers occur over time.
- For miltefosine exposure, initial adaptations come from mutations in a transporter gene, with significant aneuploidy changes appearing later as drug levels rise, highlighting that the effects of aneuploidy depend on the type and intensity of environmental stress.
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.
Leishmania, a unicellular eukaryotic parasite, is a unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored in a small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic aneuploidy (MA), might have important evolutionary and functional implications but remains under-explored due to technological limitations.
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