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Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance
The selection of parasites for drug resistance in the laboratory is an approach frequently used to investigate the mode of drug action, estimate the risk of emergence of drug resistance, or develop molecular markers for drug resistance. Here, we focused on the How rather than the Why of laboratory s...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879015/ https://www.ncbi.nlm.nih.gov/pubmed/35215248 http://dx.doi.org/10.3390/ph15020135 |
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author | Beilstein, Sabina El Phil, Radhia Sahraoui, Suzanne Sherihan Scapozza, Leonardo Kaiser, Marcel Mäser, Pascal |
author_facet | Beilstein, Sabina El Phil, Radhia Sahraoui, Suzanne Sherihan Scapozza, Leonardo Kaiser, Marcel Mäser, Pascal |
author_sort | Beilstein, Sabina |
collection | PubMed |
description | The selection of parasites for drug resistance in the laboratory is an approach frequently used to investigate the mode of drug action, estimate the risk of emergence of drug resistance, or develop molecular markers for drug resistance. Here, we focused on the How rather than the Why of laboratory selection, discussing different experimental set-ups based on research examples with Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The trypanosomatids are particularly well-suited to illustrate different strategies of selecting for drug resistance, since it was with African trypanosomes that Paul Ehrlich performed such an experiment for the first time, more than a century ago. While breakthroughs in reverse genetics and genome editing have greatly facilitated the identification and validation of candidate resistance mutations in the trypanosomatids, the forward selection of drug-resistant mutants still relies on standard in vivo models and in vitro culture systems. Critical questions are: is selection for drug resistance performed in vivo or in vitro? With the mammalian or with the insect stages of the parasites? Under steady pressure or by sudden shock? Is a mutagen used? While there is no bona fide best approach, we think that a methodical consideration of these questions provides a helpful framework for selection of parasites for drug resistance in the laboratory. |
format | Online Article Text |
id | pubmed-8879015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88790152022-02-26 Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance Beilstein, Sabina El Phil, Radhia Sahraoui, Suzanne Sherihan Scapozza, Leonardo Kaiser, Marcel Mäser, Pascal Pharmaceuticals (Basel) Review The selection of parasites for drug resistance in the laboratory is an approach frequently used to investigate the mode of drug action, estimate the risk of emergence of drug resistance, or develop molecular markers for drug resistance. Here, we focused on the How rather than the Why of laboratory selection, discussing different experimental set-ups based on research examples with Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The trypanosomatids are particularly well-suited to illustrate different strategies of selecting for drug resistance, since it was with African trypanosomes that Paul Ehrlich performed such an experiment for the first time, more than a century ago. While breakthroughs in reverse genetics and genome editing have greatly facilitated the identification and validation of candidate resistance mutations in the trypanosomatids, the forward selection of drug-resistant mutants still relies on standard in vivo models and in vitro culture systems. Critical questions are: is selection for drug resistance performed in vivo or in vitro? With the mammalian or with the insect stages of the parasites? Under steady pressure or by sudden shock? Is a mutagen used? While there is no bona fide best approach, we think that a methodical consideration of these questions provides a helpful framework for selection of parasites for drug resistance in the laboratory. MDPI 2022-01-24 /pmc/articles/PMC8879015/ /pubmed/35215248 http://dx.doi.org/10.3390/ph15020135 Text en © 2022 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 | Review Beilstein, Sabina El Phil, Radhia Sahraoui, Suzanne Sherihan Scapozza, Leonardo Kaiser, Marcel Mäser, Pascal Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance |
title | Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance |
title_full | Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance |
title_fullStr | Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance |
title_full_unstemmed | Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance |
title_short | Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance |
title_sort | laboratory selection of trypanosomatid pathogens for drug resistance |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8879015/ https://www.ncbi.nlm.nih.gov/pubmed/35215248 http://dx.doi.org/10.3390/ph15020135 |
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