Metabolite Biomarkers of <i>Leishmania</i> Antimony Resistance
<i>Leishmania</i> parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. <i>Leishmania</i> exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associa...
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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/5/1063 |
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| author | Sneider Alexander Gutierrez Guarnizo Zemfira N. Karamysheva Elkin Galeano Carlos E. Muskus |
| author_facet | Sneider Alexander Gutierrez Guarnizo Zemfira N. Karamysheva Elkin Galeano Carlos E. Muskus |
| author_sort | Sneider Alexander Gutierrez Guarnizo |
| collection | DOAJ |
| description | <i>Leishmania</i> parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. <i>Leishmania</i> exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Nevertheless, even though antimony resistance has been widely documented, the mechanisms involved are not completely understood. In this study, we aimed to identify potential metabolite biomarkers of antimony resistance that could improve leishmaniasis treatment. Here, using <i>L. tropica</i> promastigotes as the biological model, we showed that the level of response to antimony can be potentially predicted using <sup>1</sup>H-NMR-based metabolomic profiling. Antimony-resistant parasites exhibited differences in metabolite composition at the intracellular and extracellular levels, suggesting that a metabolic remodeling is required to combat the drug. Simple and time-saving exometabolomic analysis can be efficiently used for the differentiation of sensitive and resistant parasites. Our findings suggest that changes in metabolite composition are associated with an optimized response to the osmotic/oxidative stress and a rearrangement of carbon-energy metabolism. The activation of energy metabolism can be linked to the high energy requirement during the antioxidant stress response. We also found that metabolites such as proline and lactate change linearly with the level of resistance to antimony, showing a close relationship with the parasite’s efficiency of drug resistance. A list of potential metabolite biomarkers is described and discussed. |
| first_indexed | 2024-03-10T11:49:33Z |
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| id | doaj.art-c72f5c7d2c874d7e9356de1f61782fc6 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T11:49:33Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c72f5c7d2c874d7e9356de1f61782fc62023-11-21T17:52:31ZengMDPI AGCells2073-44092021-04-01105106310.3390/cells10051063Metabolite Biomarkers of <i>Leishmania</i> Antimony ResistanceSneider Alexander Gutierrez Guarnizo0Zemfira N. Karamysheva1Elkin Galeano2Carlos E. Muskus3Programa de Estudio y Control de Enfermedades Tropicales, Facultad de Medicina, Universidad de Antioquia, Medellín 050010, ColombiaDepartment of Biological Sciences, Texas Tech University, Lubbock, TX 79409, USAGrupo de Investigación en Sustancias Bioactivas-GISB, Universidad de Antioquia, Medellín 050010, ColombiaPrograma de Estudio y Control de Enfermedades Tropicales, Facultad de Medicina, Universidad de Antioquia, Medellín 050010, Colombia<i>Leishmania</i> parasites cause leishmaniasis, one of the most epidemiologically important neglected tropical diseases. <i>Leishmania</i> exhibits a high ability of developing drug resistance, and drug resistance is one of the main threats to public health, as it is associated with increased incidence, mortality, and healthcare costs. The antimonial drug is the main historically implemented drug for leishmaniasis. Nevertheless, even though antimony resistance has been widely documented, the mechanisms involved are not completely understood. In this study, we aimed to identify potential metabolite biomarkers of antimony resistance that could improve leishmaniasis treatment. Here, using <i>L. tropica</i> promastigotes as the biological model, we showed that the level of response to antimony can be potentially predicted using <sup>1</sup>H-NMR-based metabolomic profiling. Antimony-resistant parasites exhibited differences in metabolite composition at the intracellular and extracellular levels, suggesting that a metabolic remodeling is required to combat the drug. Simple and time-saving exometabolomic analysis can be efficiently used for the differentiation of sensitive and resistant parasites. Our findings suggest that changes in metabolite composition are associated with an optimized response to the osmotic/oxidative stress and a rearrangement of carbon-energy metabolism. The activation of energy metabolism can be linked to the high energy requirement during the antioxidant stress response. We also found that metabolites such as proline and lactate change linearly with the level of resistance to antimony, showing a close relationship with the parasite’s efficiency of drug resistance. A list of potential metabolite biomarkers is described and discussed.https://www.mdpi.com/2073-4409/10/5/1063leishmaniasismetabolomeproton nuclear magnetic resonance spectroscopy (<sup>1</sup>H-NMR)antimonybiomarkers of resistance leveloxidative stress balance |
| spellingShingle | Sneider Alexander Gutierrez Guarnizo Zemfira N. Karamysheva Elkin Galeano Carlos E. Muskus Metabolite Biomarkers of <i>Leishmania</i> Antimony Resistance Cells leishmaniasis metabolome proton nuclear magnetic resonance spectroscopy (<sup>1</sup>H-NMR) antimony biomarkers of resistance level oxidative stress balance |
| title | Metabolite Biomarkers of <i>Leishmania</i> Antimony Resistance |
| title_full | Metabolite Biomarkers of <i>Leishmania</i> Antimony Resistance |
| title_fullStr | Metabolite Biomarkers of <i>Leishmania</i> Antimony Resistance |
| title_full_unstemmed | Metabolite Biomarkers of <i>Leishmania</i> Antimony Resistance |
| title_short | Metabolite Biomarkers of <i>Leishmania</i> Antimony Resistance |
| title_sort | metabolite biomarkers of i leishmania i antimony resistance |
| topic | leishmaniasis metabolome proton nuclear magnetic resonance spectroscopy (<sup>1</sup>H-NMR) antimony biomarkers of resistance level oxidative stress balance |
| url | https://www.mdpi.com/2073-4409/10/5/1063 |
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