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Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host

Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), remains a significant global health challenge. The survival of M. tb in hostile extracellular and intracellular microenvironments is crucial for its pathogenicity. In this study, we discovered a Bacillus Calmette–Guérin (BCG) mutant B1033 t...

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Autores principales: Zhu, Yifan, Shi, Hongling, Tang, Tian, Li, Qianqian, Peng, Yongchong, Bermudez, Luiz E., Hu, Changmin, Chen, Huanchun, Guo, Aizhen, Chen, Yingyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670722/
https://www.ncbi.nlm.nih.gov/pubmed/37998345
http://dx.doi.org/10.3390/cells12222610
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author Zhu, Yifan
Shi, Hongling
Tang, Tian
Li, Qianqian
Peng, Yongchong
Bermudez, Luiz E.
Hu, Changmin
Chen, Huanchun
Guo, Aizhen
Chen, Yingyu
author_facet Zhu, Yifan
Shi, Hongling
Tang, Tian
Li, Qianqian
Peng, Yongchong
Bermudez, Luiz E.
Hu, Changmin
Chen, Huanchun
Guo, Aizhen
Chen, Yingyu
author_sort Zhu, Yifan
collection PubMed
description Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), remains a significant global health challenge. The survival of M. tb in hostile extracellular and intracellular microenvironments is crucial for its pathogenicity. In this study, we discovered a Bacillus Calmette–Guérin (BCG) mutant B1033 that potentially affected mycobacterium pathogenicity. This mutant contained an insertion mutation gene, fadD33, which is involved in lipid metabolism; however, its direct role in regulating M. tb infection is not well understood. Here, we found that the absence of fadD33 reduced BCG adhesion and invasion into human pulmonary alveolar epithelial cells and increased the permeability of the mycobacterial cell wall, allowing M. tb to survive in the low pH and membrane pressure extracellular microenvironment of the host cells. The absence of fadD33 also inhibited the survival of BCG in macrophages by promoting the release of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumors necrosis factor-α, through the mitogen-activated protein kinase p38 signaling pathway. Overall, these findings provide new insights into M. tb mechanisms to evade host defenses and might contribute to identifying potential therapeutic and vaccine targets for tuberculosis prevention.
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spelling pubmed-106707222023-11-11 Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host Zhu, Yifan Shi, Hongling Tang, Tian Li, Qianqian Peng, Yongchong Bermudez, Luiz E. Hu, Changmin Chen, Huanchun Guo, Aizhen Chen, Yingyu Cells Article Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), remains a significant global health challenge. The survival of M. tb in hostile extracellular and intracellular microenvironments is crucial for its pathogenicity. In this study, we discovered a Bacillus Calmette–Guérin (BCG) mutant B1033 that potentially affected mycobacterium pathogenicity. This mutant contained an insertion mutation gene, fadD33, which is involved in lipid metabolism; however, its direct role in regulating M. tb infection is not well understood. Here, we found that the absence of fadD33 reduced BCG adhesion and invasion into human pulmonary alveolar epithelial cells and increased the permeability of the mycobacterial cell wall, allowing M. tb to survive in the low pH and membrane pressure extracellular microenvironment of the host cells. The absence of fadD33 also inhibited the survival of BCG in macrophages by promoting the release of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumors necrosis factor-α, through the mitogen-activated protein kinase p38 signaling pathway. Overall, these findings provide new insights into M. tb mechanisms to evade host defenses and might contribute to identifying potential therapeutic and vaccine targets for tuberculosis prevention. MDPI 2023-11-11 /pmc/articles/PMC10670722/ /pubmed/37998345 http://dx.doi.org/10.3390/cells12222610 Text en © 2023 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
Zhu, Yifan
Shi, Hongling
Tang, Tian
Li, Qianqian
Peng, Yongchong
Bermudez, Luiz E.
Hu, Changmin
Chen, Huanchun
Guo, Aizhen
Chen, Yingyu
Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host
title Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host
title_full Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host
title_fullStr Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host
title_full_unstemmed Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host
title_short Mycobacterium tuberculosis Fatty Acyl-CoA Synthetase fadD33 Promotes Bacillus Calmette–Guérin Survival in Hostile Extracellular and Intracellular Microenvironments in the Host
title_sort mycobacterium tuberculosis fatty acyl-coa synthetase fadd33 promotes bacillus calmette–guérin survival in hostile extracellular and intracellular microenvironments in the host
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10670722/
https://www.ncbi.nlm.nih.gov/pubmed/37998345
http://dx.doi.org/10.3390/cells12222610
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