Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophages
Mycobacterium abscessus (Mab), a nontuberculous mycobacterium, is increasing in prevalence worldwide and causes treatment-refractory pulmonary diseases. However, how Mab rewires macrophage energy metabolism to facilitate its survival is poorly understood. We compared the metabolic profiles of murine...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2025.2454323 |
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| author | Ho Won Kim Ji Won Lee Hoe Sun Yoon Hwan-Woo Park Young Ik Lee Sung Ki Lee Jake Whang Jong-Seok Kim |
| author_facet | Ho Won Kim Ji Won Lee Hoe Sun Yoon Hwan-Woo Park Young Ik Lee Sung Ki Lee Jake Whang Jong-Seok Kim |
| author_sort | Ho Won Kim |
| collection | DOAJ |
| description | Mycobacterium abscessus (Mab), a nontuberculous mycobacterium, is increasing in prevalence worldwide and causes treatment-refractory pulmonary diseases. However, how Mab rewires macrophage energy metabolism to facilitate its survival is poorly understood. We compared the metabolic profiles of murine bone marrow-derived macrophages (BMDMs) infected with smooth (S)- and rough (R)-type Mab using extracellular flux technology. Mab infection shifted BMDMs towards a more energetic phenotype, marked by increased oxidative phosphorylation (OXPHOS) and glycolysis, with a significantly greater enhancement in OXPHOS. This metabolic adaptation was characterized by enhanced ATP production rates, particularly in cells infected with S-type Mab, highlighting OXPHOS as a key energy source. Notably, Mab infection also modulated mitochondrial substrate preferences, increasing fatty acid oxidation capabilities while revealing significant changes in glutamine dependency and flexibility. R-type Mab infections exhibited a marked decrease in glutamine reliance but enhanced metabolic flexibility and capacity. Furthermore, targeting metabolic pathways related to glutamine and fatty acid oxidation exacerbated Mab growth within macrophages, suggesting these pathways play a protective role against infection. These insights advance our understanding of Mab’s impact on host cell metabolism and propose a novel avenue for therapeutic intervention. By manipulating host mitochondrial metabolism, we identify a potential host-directed therapeutic strategy against Mab, offering a promising alternative to conventional treatments beleaguered by drug resistance. This study underscores the importance of exploring metabolic interventions to combat Mab infection, paving the way for innovative approaches in the fight against this formidable pathogen. |
| format | Article |
| id | doaj-art-745ee8dcebe8407dbedab42a529e2d90 |
| institution | Kabale University |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-745ee8dcebe8407dbedab42a529e2d902025-01-20T04:52:02ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2025.2454323Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophagesHo Won Kim0Ji Won Lee1Hoe Sun Yoon2Hwan-Woo Park3Young Ik Lee4Sung Ki Lee5Jake Whang6Jong-Seok Kim7Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, South KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, South KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, South KoreaDepartment of Cell Biology, Konyang University Hospital and College of Medicine, Daejeon, South KoreaLee’s Biotech Co, Daejeon, South KoreaDepartment of Obstetrics and Gynecology, Konyang University Hospital, Daejeon, South KoreaKorea Mycobacterium Resource Center (KMRC), Department of Research and Development, The Korean Institute of Tuberculosis, Osong, South KoreaMyunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, South KoreaMycobacterium abscessus (Mab), a nontuberculous mycobacterium, is increasing in prevalence worldwide and causes treatment-refractory pulmonary diseases. However, how Mab rewires macrophage energy metabolism to facilitate its survival is poorly understood. We compared the metabolic profiles of murine bone marrow-derived macrophages (BMDMs) infected with smooth (S)- and rough (R)-type Mab using extracellular flux technology. Mab infection shifted BMDMs towards a more energetic phenotype, marked by increased oxidative phosphorylation (OXPHOS) and glycolysis, with a significantly greater enhancement in OXPHOS. This metabolic adaptation was characterized by enhanced ATP production rates, particularly in cells infected with S-type Mab, highlighting OXPHOS as a key energy source. Notably, Mab infection also modulated mitochondrial substrate preferences, increasing fatty acid oxidation capabilities while revealing significant changes in glutamine dependency and flexibility. R-type Mab infections exhibited a marked decrease in glutamine reliance but enhanced metabolic flexibility and capacity. Furthermore, targeting metabolic pathways related to glutamine and fatty acid oxidation exacerbated Mab growth within macrophages, suggesting these pathways play a protective role against infection. These insights advance our understanding of Mab’s impact on host cell metabolism and propose a novel avenue for therapeutic intervention. By manipulating host mitochondrial metabolism, we identify a potential host-directed therapeutic strategy against Mab, offering a promising alternative to conventional treatments beleaguered by drug resistance. This study underscores the importance of exploring metabolic interventions to combat Mab infection, paving the way for innovative approaches in the fight against this formidable pathogen.https://www.tandfonline.com/doi/10.1080/21505594.2025.2454323Mycobacterium abscessusmetabolismglycolysisOXPHOS |
| spellingShingle | Ho Won Kim Ji Won Lee Hoe Sun Yoon Hwan-Woo Park Young Ik Lee Sung Ki Lee Jake Whang Jong-Seok Kim Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophages Virulence Mycobacterium abscessus metabolism glycolysis OXPHOS |
| title | Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophages |
| title_full | Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophages |
| title_fullStr | Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophages |
| title_full_unstemmed | Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophages |
| title_short | Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophages |
| title_sort | restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of mycobacterium abscessus in macrophages |
| topic | Mycobacterium abscessus metabolism glycolysis OXPHOS |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2025.2454323 |
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