PUBLICATION

Early cell-autonomous accumulation of neutral lipids during infection promotes mycobacterial growth

Authors
McClean, C.M., Tobin, D.M.
ID
ZDB-PUB-200515-8
Date
2020
Source
PLoS One   15: e0232251 (Journal)
Registered Authors
McClean, Colleen, Tobin, David
Keywords
none
MeSH Terms
  • Ezetimibe/pharmacology
  • Lipid Metabolism*
  • Macrophages/metabolism
  • Macrophages/microbiology
  • Mutation
  • Mycobacterium marinum/drug effects
  • Mycobacterium marinum/genetics
  • Mycobacterium marinum/growth & development*
  • Mycobacterium marinum/physiology
  • Operon/genetics
PubMed
32407412 Full text @ PLoS One
Abstract
Lipids represent an important source of nutrition for infecting mycobacteria, accumulating within the necrotic core of granulomas and present in foamy macrophages associated with mycobacterial infection. In order to better understand the timing, process and importance of lipid accumulation, we developed methods for direct in vivo visualization and quantification of this process using the zebrafish-M. marinum larval model of infection. We find that neutral lipids accumulate cell-autonomously in mycobacterium-infected macrophages in vivo during early infection, with detectable levels of accumulation by two days post-infection. Treatment with ezetimibe, an FDA-approved drug, resulted in decreased levels of free cholesterol and neutral lipids, and a reduction of bacterial growth in vivo. The effect of ezetimibe in reducing bacterial growth was dependent on the mce4 operon, a key bacterial determinant of lipid utilization. Thus, in vivo, lipid accumulation can occur cell-autonomously at early timepoints of mycobacterial infection, and limitation of this process results in decreased bacterial burden.
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