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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • McClean, CM; Tobin, DM

Published Date

  • 2020

Published In

Volume / Issue

  • 15 / 5

Start / End Page

  • e0232251 -

PubMed ID

  • 32407412

Pubmed Central ID

  • 32407412

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0232251

Language

  • eng

Conference Location

  • United States