التفاصيل البيبلوغرافية
| العنوان: |
Impaired fatty acid import or catabolism in macrophages restricts intracellular growth of Mycobacterium tuberculosis. |
| المؤلفون: |
Simwela NV, Jaecklein E, Sassetti CM, Russell DGM |
| المصدر: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 01. Date of Electronic Publication: 2024 Sep 01. |
| نوع المنشور: |
Journal Article; Preprint |
| اللغة: |
English |
| بيانات الدورية: |
Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: |
Mycobacterium tuberculosis (Mtb) infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular Mtb utilize host derived lipids to maintain infection, the role of macrophage lipid processing on the bacterias ability to access the intracellular lipid pool remains undefined. We utilized a CRISPR-Cas9 genetic approach to assess the impact of sequential steps in fatty acid metabolism on the growth of intracellular Mtb. Our analyzes demonstrate that macrophages which cannot either import, store or catabolize fatty acids restrict Mtb growth by both common and divergent anti-microbial mechanisms, including increased glycolysis, increased oxidative stress, production of pro-inflammatory cytokines, enhanced autophagy and nutrient limitation. We also show that impaired macrophage lipid droplet biogenesis is restrictive to Mtb replication, but increased induction of the same fails to rescue Mtb growth. Our work expands our understanding of how host fatty acid homeostasis impacts Mtb growth in the macrophage. |
| معلومات مُعتمدة: |
R01 AI155319 United States AI NIAID NIH HHS; S10 OD032135 United States OD NIH HHS; T32 AI007349 United States AI NIAID NIH HHS; U19 AI162598 United States AI NIAID NIH HHS |
| تواريخ الأحداث: |
Date Created: 20240802 Latest Revision: 20240904 |
| رمز التحديث: |
20240904 |
| مُعرف محوري في PubMed: |
PMC11291043 |
| DOI: |
10.1101/2024.07.22.604660 |
| PMID: |
39091727 |
| قاعدة البيانات: |
MEDLINE |
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