biostudies-literatureUnknownSimwela NVNIAID NIH HHSNIH HHS<i>Mycobacterium tuberculosis (Mtb)</i> infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular <i>Mtb</i> utilize host derived lipids to maintain infection, the role of macrophage lipid processing on the bacteria's 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 <i>Mtb</i>. Our analyzes demonstrate that macrophages which cannot either import, store or catabolize fatty acids restrict <i>Mtb</i> growth by both common and divergent anti-microbial mechanisms, including increased glycolysis, increased oxidative stress, production of pro-inflammatory cytokines, enhancbioRxiv : the preprint server for biology2024.07.22.604660https://www.ebi.ac.uk/biostudies/studies/S-EPMC11291043biostudies-literatureImpaired fatty acid import or catabolism in macrophages restricts intracellular growth of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;.PMC11291043S10 OD032135R01 AI155319U19 AI162598T32 AI007349Simwela NVSassetti CMJaecklein ERussell DGfalseImpaired fatty acid import or catabolism in macrophages restricts intracellular growth of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt;.<i>Mycobacterium tuberculosis (Mtb)</i> infection of macrophages reprograms cellular metabolism to promote lipid retention. While it is clearly known that intracellular <i>Mtb</i> utilize host derived lipids to maintain infection, the role of macrophage lipid processing on the bacteria's 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 <i>Mtb</i>. Our analyzes demonstrate that macrophages which cannot either import, store or catabolize fatty acids restrict <i>Mtb</i> growth by both common and divergent anti-microbial mechanisms, including increased glycolysis, increased oxidative stress, production of pro-inflammatory cytokines, enhanc2025-01-01T00:00:00Z2025 Jan2026-06-30T03:19:35.553Z2025-04-06T01:57:07.037ZS-EPMC112910433909172710.1101/2024.07.22.604660