PUBLICATION
Mycobacterium marinum phthiocerol dimycocerosates enhance macrophage phagosomal permeabilization and membrane damage
- Authors
- Osman, M.M., Pagán, A.J., Shanahan, J.K., Ramakrishnan, L.
- ID
- ZDB-PUB-200724-26
- Date
- 2020
- Source
- PLoS One 15: e0233252 (Journal)
- Registered Authors
- Ramakrishnan, Lalita
- Keywords
- none
- MeSH Terms
-
- Cell Line
- Cell Membrane/drug effects*
- Cell Membrane/metabolism*
- Humans
- Lipids/pharmacology*
- Macrophages/cytology*
- Macrophages/drug effects
- Mycobacterium marinum/metabolism*
- Mycobacterium marinum/physiology
- Permeability/drug effects
- Phagosomes/drug effects*
- Phagosomes/metabolism
- PubMed
- 32701962 Full text @ PLoS One
Citation
Osman, M.M., Pagán, A.J., Shanahan, J.K., Ramakrishnan, L. (2020) Mycobacterium marinum phthiocerol dimycocerosates enhance macrophage phagosomal permeabilization and membrane damage. PLoS One. 15:e0233252.
Abstract
Phthiocerol dimycocerosates (PDIMs) are a class of mycobacterial lipids that promote virulence in Mycobacterium tuberculosis and Mycobacterium marinum. It has recently been shown that PDIMs work in concert with the M. tuberculosis Type VII secretion system ESX-1 to permeabilize the phagosomal membranes of infected macrophages. As the zebrafish-M. marinum model of infection has revealed the critical role of PDIM at the host-pathogen interface, we set to determine if PDIMs contributed to phagosomal permeabilization in M. marinum. Using an ΔmmpL7 mutant defective in PDIM transport, we find the PDIM-ESX-1 interaction to be conserved in an M. marinum macrophage infection model. However, we find PDIM and ESX-1 mutants differ in their degree of defect, with the PDIM mutant retaining more membrane damaging activity. Using an in vitro hemolysis assay-a common surrogate for cytolytic activity, we find that PDIM and ESX-1 differ in their contributions: the ESX-1 mutant loses hemolytic activity while PDIM retains it. Our observations confirm the involvement of PDIMs in phagosomal permeabilization in M. marinum infection and suggest that PDIM enhances the membrane disrupting activity of pathogenic mycobacteria and indicates that the role they play in damaging phagosomal and red blood cell membranes may differ.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping