<i>Mycobacterium tuberculosis</i> <i>whiB3</i> and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress
The physiological state of the human macrophage may impact the metabolism and the persistence of <i>Mycobacterium tuberculosis</i>. This pathogen senses and counters the levels of O<sub>2</sub>, CO, reactive oxygen species (ROS), and pH in macrophages. <i>M. tuberculosi...
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MDPI AG
2022-09-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/9/1821 |
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| author | Omar M. Barrientos Elizabeth Langley Yolanda González Carlos Cabello Martha Torres Silvia Guzmán-Beltrán |
| author_facet | Omar M. Barrientos Elizabeth Langley Yolanda González Carlos Cabello Martha Torres Silvia Guzmán-Beltrán |
| author_sort | Omar M. Barrientos |
| collection | DOAJ |
| description | The physiological state of the human macrophage may impact the metabolism and the persistence of <i>Mycobacterium tuberculosis</i>. This pathogen senses and counters the levels of O<sub>2</sub>, CO, reactive oxygen species (ROS), and pH in macrophages. <i>M. tuberculosis</i> responds to oxidative stress through WhiB3. The goal was to determine the effect of NADPH oxidase (NOX) modulation and oxidative agents on the expression of <i>whiB3</i> and genes involved in lipid metabolism (<i>lip-Y</i>, <i>Icl-1</i>, and <i>tgs-1</i>) in intracellular mycobacteria. Human macrophages were first treated with NOX modulators such as DPI (ROS inhibitor) and PMA (ROS activator), or with oxidative agents (H<sub>2</sub>O<sub>2</sub> and generator system O<sub>2</sub><sup>•−</sup>), and then infected with mycobacteria. We determined ROS production, cell viability, and expression of <i>whiB3</i>, as well as genes involved in lipid metabolism. PMA, H<sub>2</sub>O<sub>2</sub>, and O<sub>2</sub><sup>•−</sup> increased ROS production in human macrophages, generating oxidative stress in bacteria and augmented the gene expression of <i>whiB3</i>, <i>lip-Y</i>, <i>Icl-1</i>, and <i>tgs-1</i>. Our results suggest that ROS production in macrophages induces oxidative stress in intracellular bacteria inducing <i>whiB3</i> expression. This factor may activate the synthesis of reserve lipids produced to survive in the latency state, which allows its persistence for long periods within the host. |
| first_indexed | 2024-03-09T23:05:51Z |
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| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T23:05:51Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-62ce71ab2e7e470db99dd1e4f9b7f8402023-11-23T17:53:47ZengMDPI AGMicroorganisms2076-26072022-09-01109182110.3390/microorganisms10091821<i>Mycobacterium tuberculosis</i> <i>whiB3</i> and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative StressOmar M. Barrientos0Elizabeth Langley1Yolanda González2Carlos Cabello3Martha Torres4Silvia Guzmán-Beltrán5Departamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Sección XVI, Alcaldía de Tlalpan, Mexico City 14080, MexicoDepartamento de Investigación Básica, Instituto Nacional de Cancerología, Mexico City 14080, MexicoDepartamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Sección XVI, Alcaldía de Tlalpan, Mexico City 14080, MexicoDepartamento de Virologia y Micologia, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, MexicoLaboratorio de Inmunobiología de la Tuberculosis, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Mexico City 14080, MexicoDepartamento de Investigación en Microbiología, Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas, Calzada de Tlalpan 4502, Sección XVI, Alcaldía de Tlalpan, Mexico City 14080, MexicoThe physiological state of the human macrophage may impact the metabolism and the persistence of <i>Mycobacterium tuberculosis</i>. This pathogen senses and counters the levels of O<sub>2</sub>, CO, reactive oxygen species (ROS), and pH in macrophages. <i>M. tuberculosis</i> responds to oxidative stress through WhiB3. The goal was to determine the effect of NADPH oxidase (NOX) modulation and oxidative agents on the expression of <i>whiB3</i> and genes involved in lipid metabolism (<i>lip-Y</i>, <i>Icl-1</i>, and <i>tgs-1</i>) in intracellular mycobacteria. Human macrophages were first treated with NOX modulators such as DPI (ROS inhibitor) and PMA (ROS activator), or with oxidative agents (H<sub>2</sub>O<sub>2</sub> and generator system O<sub>2</sub><sup>•−</sup>), and then infected with mycobacteria. We determined ROS production, cell viability, and expression of <i>whiB3</i>, as well as genes involved in lipid metabolism. PMA, H<sub>2</sub>O<sub>2</sub>, and O<sub>2</sub><sup>•−</sup> increased ROS production in human macrophages, generating oxidative stress in bacteria and augmented the gene expression of <i>whiB3</i>, <i>lip-Y</i>, <i>Icl-1</i>, and <i>tgs-1</i>. Our results suggest that ROS production in macrophages induces oxidative stress in intracellular bacteria inducing <i>whiB3</i> expression. This factor may activate the synthesis of reserve lipids produced to survive in the latency state, which allows its persistence for long periods within the host.https://www.mdpi.com/2076-2607/10/9/1821<i>Mycobacterium tuberculosis</i>oxidative stressWhiB3lipid metabolism |
| spellingShingle | Omar M. Barrientos Elizabeth Langley Yolanda González Carlos Cabello Martha Torres Silvia Guzmán-Beltrán <i>Mycobacterium tuberculosis</i> <i>whiB3</i> and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress Microorganisms <i>Mycobacterium tuberculosis</i> oxidative stress WhiB3 lipid metabolism |
| title | <i>Mycobacterium tuberculosis</i> <i>whiB3</i> and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress |
| title_full | <i>Mycobacterium tuberculosis</i> <i>whiB3</i> and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress |
| title_fullStr | <i>Mycobacterium tuberculosis</i> <i>whiB3</i> and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress |
| title_full_unstemmed | <i>Mycobacterium tuberculosis</i> <i>whiB3</i> and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress |
| title_short | <i>Mycobacterium tuberculosis</i> <i>whiB3</i> and Lipid Metabolism Genes Are Regulated by Host Induced Oxidative Stress |
| title_sort | i mycobacterium tuberculosis i i whib3 i and lipid metabolism genes are regulated by host induced oxidative stress |
| topic | <i>Mycobacterium tuberculosis</i> oxidative stress WhiB3 lipid metabolism |
| url | https://www.mdpi.com/2076-2607/10/9/1821 |
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