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
Citation
McClean, C.M., Tobin, D.M. (2020) Early cell-autonomous accumulation of neutral lipids during infection promotes mycobacterial growth. PLoS One. 15:e0232251.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping