Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis DOI Open Access
Nelson V. Simwela, Eleni Jaecklein, Christopher M. Sassetti

et al.

Published: Dec. 16, 2024

Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate mutated cannot either import, store or catabolize acids restrict by both common and divergent anti-microbial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction fails rescue growth. work expands our understanding how homeostasis impacts macrophage.

Language: Английский

Advances in Host–Pathogen Interactions in Tuberculosis: Emerging Strategies for Therapeutic Intervention DOI Open Access
Mohammad Javad Nasiri, Vishwanath Venketaraman

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1621 - 1621

Published: Feb. 14, 2025

Tuberculosis (TB) remains one of the most challenging infectious diseases, with Mycobacterium tuberculosis (Mtb) employing sophisticated mechanisms to evade host immunity and establish persistent infections. This review explores recent advances in understanding Mtb's immune evasion strategies; granuloma dynamics; emerging immunotherapeutic approaches. Key findings highlight manipulation autophagy; metabolic reprogramming; cytokine pathways by Mtb sustain its survival within cells. Insights into formation reveal critical role bacterial lipids; modulation; hypoxia-driven dormancy maintaining chronic infection. Innovative therapeutic strategies, including host-directed therapies; epigenetic interventions; immunomodulators, hold promise for improving TB management combating drug-resistant strains. Despite these advancements, significant challenges remain, development effective vaccines; addressing latent TB; ensuring equitable access novel treatments. The integration advanced technologies such as artificial intelligence multi-omics approaches, alongside global collaboration, is essential overcome hurdles. underscores importance a multidisciplinary approach tackling TB, ultimate goal eradicating this health threat.

Language: Английский

Citations

1
Mycobacteria Exploit Host GPR84 to Dampen Pro-Inflammatory Responses and Promote Infection in Macrophages DOI Creative Commons
Reziya Wumaier, Ke Zhang, Jing Zhou

et al.

Microorganisms, Journal Year: 2025, Volume and Issue: 13(1), P. 110 - 110

Published: Jan. 8, 2025

Tuberculosis (TB) remains the major cause of mortality and morbidity, causing approximately 1.3 million deaths annually. As a highly successful pathogen, Mycobacterium tuberculosis (Mtb) has evolved numerous strategies to evade host immune responses, making it essential understand interactions between Mtb cells. G-protein-coupled receptor 84 (GPR84), member family, contributes regulation pro-inflammatory reactions migration innate cells, such as macrophages. Its role in mycobacterial infection, however, not yet been explored. We found that GPR84 is induced whole blood samples from patients marinum (Mm)-infected macrophage models. Using Mm-wasabi infection model mouse tails, we an important determinant extent tissue damage. Furthermore, our studies vitro Mm model, appears inhibits cytokines expression increases intracellular lipid droplet (LD) accumulation, thereby promoting bacterial survival. Our findings suggest could be potential therapeutic target for host-directed anti-TB therapeutics.

Language: Английский

Citations

0
Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis DOI Open Access
Nelson V. Simwela, Eleni Jaecklein, Christopher M. Sassetti

et al.

Published: Feb. 20, 2025

Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate which cannot either import, store or catabolize acids restrict by both common and divergent anti-microbial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction same fails rescue growth. work expands our understanding how homeostasis impacts macrophage.

Language: Английский

Citations

0
Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis DOI Creative Commons
Nelson V. Simwela, Eleni Jaecklein, Christopher M. Sassetti

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: March 13, 2025

Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host-derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyses demonstrate cannot either import, store, or catabolize acids restrict by both common and divergent antimicrobial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy, nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction same fails rescue growth. work expands our understanding how host homeostasis impacts macrophage.

Language: Английский

Citations

0
Subtractive Genomics for Identifying Tuberculosis-Linked Bacterial Targets in Type-2 Diabetes and Drug Repurposing Strategies DOI
Md. Kaderi Kibria,

Jannatul Nayem Fariha,

Most. Nusrat Jahan Resma

et al.

Next research., Journal Year: 2025, Volume and Issue: unknown, P. 100377 - 100377

Published: May 1, 2025

Language: Английский

Citations

0
Uncharted territory: the role of mitochondrial DNA variation in macrophage-mediated host susceptibility to tuberculosis DOI Creative Commons
Dayna Croock, Yolandi Swart, Tomasz Janusz Sanko

et al.

Tuberculosis, Journal Year: 2025, Volume and Issue: 153, P. 102650 - 102650

Published: May 8, 2025

Language: Английский

Citations

0
Impaired fatty acid import or catabolism in macrophages restricts intracellular growth ofMycobacterium tuberculosis DOI Creative Commons
Nelson V. Simwela, Eleni Jaecklein, Christopher M. Sassetti

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 23, 2024

Abstract Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate which cannot either import, store or catabolize acids restrict by both common and divergent anti-microbial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction same fails rescue growth. work expands our understanding how homeostasis impacts macrophage.

Language: Английский

Citations

1
Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis DOI Creative Commons
Nelson V. Simwela, Eleni Jaecklein, Christopher M. Sassetti

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Dec. 16, 2024

Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host-derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyses demonstrate cannot either import, store, or catabolize acids restrict by both common and divergent antimicrobial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy, nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction same fails rescue growth. work expands our understanding how host homeostasis impacts macrophage.

Language: Английский

Citations

0
Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis DOI Open Access
Nelson V. Simwela, Eleni Jaecklein, Christopher M. Sassetti

et al.

Published: Dec. 16, 2024

Mycobacterium tuberculosis ( Mtb ) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular utilize host derived lipids maintain infection, the role macrophage processing on bacteria’s ability access pool remains undefined. We utilized a CRISPR-Cas9 genetic approach assess impact sequential steps in fatty acid growth . Our analyzes demonstrate mutated cannot either import, store or catabolize acids restrict by both common and divergent anti-microbial mechanisms, including increased glycolysis, oxidative stress, production pro-inflammatory cytokines, enhanced autophagy nutrient limitation. also show impaired droplet biogenesis restrictive replication, but induction fails rescue growth. work expands our understanding how homeostasis impacts macrophage.

Language: Английский

Citations

0