Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism
UMass Chan AffiliationsDepartment of Biochemistry and Molecular Pharmacology
RNA Therapeutics Institute
KeywordsBacterial immune evasion
Biochemistry, Biophysics, and Structural Biology
Cell and Developmental Biology
Genetics and Genomics
Immunology and Infectious Disease
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AbstractMycobacterium tuberculosis (Mtb) survives in macrophages by evading delivery to the lysosome and promoting the accumulation of lipid bodies, which serve as a bacterial source of nutrients. We found that by inducing the microRNA (miRNA) miR-33 and its passenger strand miR-33*, Mtb inhibited integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation to support bacterial replication. Silencing of miR-33 and miR-33* by genetic or pharmacological means promoted autophagy flux through derepression of key autophagy effectors (such as ATG5, ATG12, LC3B and LAMP1) and AMPK-dependent activation of the transcription factors FOXO3 and TFEB, which enhanced lipid catabolism and Mtb xenophagy. These data define a mammalian miRNA circuit used by Mtb to coordinately inhibit autophagy and reprogram host lipid metabolism to enable intracellular survival and persistence in the host.
Nat Immunol. 2016 Jun;17(6):677-86. doi: 10.1038/ni.3434. Epub 2016 Apr 18. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/48804
Full list of authors omitted for brevity. For full list see article.