High-throughput screening of small molecules targeting <i>Mycobacterium tuberculosis</i> in human iPSC macrophages

New treatments are still necessary to eradicate tuberculosis disease. Macrophages derived from human induced pluripotent stem cells (hiPSC-Macs) offer a physiological niche to identify potential new drugs in the context of <i>Mycobacterium tuberculosis</i> (Mtb) infection. Here, we describe the scale-up of hiPSC-Macs production in 5-stack chambers for high-throughput drug screening against Mtb. A rate of approximately 100 million hiPSC-Macs was generated with optimal quality for a period of up to 12 weeks. Moreover, the infection model was optimized using a luminescence-based Mtb reporter strain. The assay showed enough sensitivity to identify compounds that could target host-pathogen interactions during Mtb infection. We interrogated a library of 200,000 compounds in Mtb-infected hiPSC-Macs with a Z-score above 0.3 in all plates analyzed. After secondary assays, 223 qualified hits were selected for further progression.

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Publication Details

Journal
Antimicrobial Agents and Chemotherapy
Published
2025-05-27
DOI
https://doi.org/10.1128/aac.01613-24
Citations
3
Primary Topic
bioluminescence and chemiluminescence research
Type
article
Field-Weighted Citation Impact
2.42

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article

High-throughput screening of small molecules targeting Mycobacterium tuberculosis in human iPSC macrophages

Laura Padrón-Barthe, Helena Garuti, Esther Pérez‐Herrán, Modesto J. Remuiñán et al.
3 citations
Antimicrobial Agents and Chemotherapy
bioluminescence and chemiluminescence research
2.42
article

High-throughput screening of small molecules targeting Mycobacterium tuberculosis in human iPSC macrophages

Laura Padrón-Barthe, Helena Garuti, Esther Pérez‐Herrán, Modesto J. Remuiñán, María Martínez-Hoyos, Charlotte Ashby, Delfina Segura-Carro, Alfonso Mendoza-Losana, Eugenia Meiler, Sara Viera-Morilla, Rubén González-del-Rio, Lisa Mohamet, Beatriz Rodríguez-Miquel, Delia Blanco, Laura Pérez, Vanesa Gómez, Alejandro Armesilla-Diaz, María Pilar Arenaz, Emiliana D'Oria
article en
3 citations

Abstract

New treatments are still necessary to eradicate tuberculosis disease. Macrophages derived from human induced pluripotent stem cells (hiPSC-Macs) offer a physiological niche to identify potential new drugs in the context of <i>Mycobacterium tuberculosis</i> (Mtb) infection. Here, we describe the scale-up of hiPSC-Macs production in 5-stack chambers for high-throughput drug screening against Mtb. A rate of approximately 100 million hiPSC-Macs was generated with optimal quality for a period of up to 12 weeks. Moreover, the infection model was optimized using a luminescence-based Mtb reporter strain. The assay showed enough sensitivity to identify compounds that could target host-pathogen interactions during Mtb infection. We interrogated a library of 200,000 compounds in Mtb-infected hiPSC-Macs with a Z-score above 0.3 in all plates analyzed. After secondary assays, 223 qualified hits were selected for further progression.

Antimicrobial Agents and ChemotherapyVol. 69(7)
Age UK (GB), GlaxoSmithKline (India) (IN), GlaxoSmithKline (France) (FR), GlaxoSmithKline (United States) (US), GlaxoSmithKline (Spain) (ES)
Ministerio de Ciencia, Innovación y Universidades, European Commission
Good health and well-being
Openalex Percentile: Top 12%
bioluminescence and chemiluminescence research
2.42
DOIOpen Access PDFOpenAlex
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