Phenotypic assays for Mycobacterium tuberculosis infection
Autor: | Vincent Delorme, Alain R. Baulard, Frank Lafont, Elisabeth Werkmeister, Nathalie Deboosere, Gaspard Deloison, Raffaella Iantomasi, Ok-Ryul Song, Christophe J. Queval, Priscille Brodin |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Histology Tuberculosis biology Drug discovery Intracellular parasite 030106 microbiology Cell Biology biology.organism_classification medicine.disease Virology Phenotype 3. Good health Pathology and Forensic Medicine Microbiology Mycobacterium tuberculosis 03 medical and health sciences 030104 developmental biology Drug development medicine Axenic Intracellular |
Zdroj: | Cytometry Part A. 91:983-994 |
ISSN: | 1552-4922 |
DOI: | 10.1002/cyto.a.23129 |
Popis: | Tuberculosis (TB) is still a major global threat, killing more than one million persons each year. With the constant increase of Mycobacterium tuberculosis strains resistant to first- and second-line drugs, there is an urgent need for the development of new drugs to control the propagation of TB. Although screenings of small molecules on axenic M. tuberculosis cultures were successful for the identification of novel putative anti-TB drugs, new drugs in the development pipeline remains scarce. Host-directed therapy may represent an alternative for drug development against TB. Indeed, M. tuberculosis has multiple specific interactions within host phagocytes, which may be targeted by small molecules. In order to enable drug discovery strategies against microbes residing within host macrophages, we developed multiple fluorescence-based HT/CS phenotypic assays monitoring the intracellular replication of M. tuberculosis as well as its intracellular trafficking. What we propose here is a population-based, multi-parametric analysis pipeline that can be used to monitor the intracellular fate of M. tuberculosis and the dynamics of cellular events such as phagosomal maturation (acidification and permeabilization), zinc poisoning system or lipid body accumulation. Such analysis allows the quantification of biological events considering the host-pathogen interplay and may thus be derived to other intracellular pathogens. © 2017 International Society for Advancement of Cytometry. |
Databáze: | OpenAIRE |
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