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Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models
Cutaneous leishmaniasis (CL) is the most common disease form caused by a Leishmania parasite infection and considered a neglected tropical disease (NTD), affecting 700,000 to 1.2 million new cases per year in the world. Leishmania major is one of several different species of the Leishmania genus tha...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152770/ https://www.ncbi.nlm.nih.gov/pubmed/34068119 http://dx.doi.org/10.3390/pathogens10050593 |
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author | Parab, Adwaita R. Thomas, Diane Lostracco-Johnson, Sharon Siqueira-Neto, Jair L. McKerrow, James H. Dorrestein, Pieter C. McCall, Laura-Isobel |
author_facet | Parab, Adwaita R. Thomas, Diane Lostracco-Johnson, Sharon Siqueira-Neto, Jair L. McKerrow, James H. Dorrestein, Pieter C. McCall, Laura-Isobel |
author_sort | Parab, Adwaita R. |
collection | PubMed |
description | Cutaneous leishmaniasis (CL) is the most common disease form caused by a Leishmania parasite infection and considered a neglected tropical disease (NTD), affecting 700,000 to 1.2 million new cases per year in the world. Leishmania major is one of several different species of the Leishmania genus that can cause CL. Current CL treatments are limited by adverse effects and rising resistance. Studying disease metabolism at the site of infection can provide knowledge of new targets for host-targeted drug development. In this study, tissue samples were collected from mice infected in the ear or footpad with L. major and analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differences in overall metabolite profiles were noted in the ear at the site of the lesion. Interestingly, lesion-adjacent, macroscopically healthy sites also showed alterations in specific metabolites, including selected glycerophosphocholines (PCs). Host-derived PCs in the lower m/z range (m/z 200–799) showed an increase with infection in the ear at the lesion site, while those in the higher m/z range (m/z 800–899) were decreased with infection at the lesion site. Overall, our results expanded our understanding of the mechanisms of CL pathogenesis through host metabolism and may lead to new curative measures against infection with Leishmania. |
format | Online Article Text |
id | pubmed-8152770 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81527702021-05-27 Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models Parab, Adwaita R. Thomas, Diane Lostracco-Johnson, Sharon Siqueira-Neto, Jair L. McKerrow, James H. Dorrestein, Pieter C. McCall, Laura-Isobel Pathogens Article Cutaneous leishmaniasis (CL) is the most common disease form caused by a Leishmania parasite infection and considered a neglected tropical disease (NTD), affecting 700,000 to 1.2 million new cases per year in the world. Leishmania major is one of several different species of the Leishmania genus that can cause CL. Current CL treatments are limited by adverse effects and rising resistance. Studying disease metabolism at the site of infection can provide knowledge of new targets for host-targeted drug development. In this study, tissue samples were collected from mice infected in the ear or footpad with L. major and analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differences in overall metabolite profiles were noted in the ear at the site of the lesion. Interestingly, lesion-adjacent, macroscopically healthy sites also showed alterations in specific metabolites, including selected glycerophosphocholines (PCs). Host-derived PCs in the lower m/z range (m/z 200–799) showed an increase with infection in the ear at the lesion site, while those in the higher m/z range (m/z 800–899) were decreased with infection at the lesion site. Overall, our results expanded our understanding of the mechanisms of CL pathogenesis through host metabolism and may lead to new curative measures against infection with Leishmania. MDPI 2021-05-13 /pmc/articles/PMC8152770/ /pubmed/34068119 http://dx.doi.org/10.3390/pathogens10050593 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Parab, Adwaita R. Thomas, Diane Lostracco-Johnson, Sharon Siqueira-Neto, Jair L. McKerrow, James H. Dorrestein, Pieter C. McCall, Laura-Isobel Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models |
title | Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models |
title_full | Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models |
title_fullStr | Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models |
title_full_unstemmed | Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models |
title_short | Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models |
title_sort | dysregulation of glycerophosphocholines in the cutaneous lesion caused by leishmania major in experimental murine models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152770/ https://www.ncbi.nlm.nih.gov/pubmed/34068119 http://dx.doi.org/10.3390/pathogens10050593 |
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