The Rhodococcus equi virulence protein VapA disrupts endolysosome function and stimulates lysosome biogenesis
Adam P Rofe1, Luther J Davis2, Jean L Whittingham3
1Department of Biology, Wentworth Way, University of York, York, UK.
Microbiologyopen
|October 21, 2016
Summary
Rhodococcus equi virulence protein VapA disrupts foal macrophage endolysosomes, impairing their function. This mechanism helps the bacterium survive by evading lysosomal degradation.
Area of Science:
- Microbiology
- Cell Biology
- Veterinary Pathology
Background:
- Rhodococcus equi (R. equi) is a significant cause of foal mortality.
- R. equi possesses a virulence plasmid encoding virulence-associated proteins (Vaps).
- VapA is crucial for R. equi's intracellular survival within macrophages, but its function is poorly understood.
Purpose of the Study:
- To elucidate the precise function of VapA in host-pathogen interactions.
- To investigate the impact of VapA on macrophage endolysosomal pathways.
Main Methods:
- Cellular analysis of VapA-treated macrophages.
- Biochemical assays to assess endolysosomal enzyme activity.
- Immunofluorescence microscopy to detect organelle markers (LBPA, LC3, Rab7).
Main Results:
- VapA induces swelling and functional impairment of late endosomes and lysosomes.
- Reduced Cathepsin B activity and accumulation of LBPA, LC3, and Rab7 observed in affected organelles.
- Cells compensate by upregulating lysosome biogenesis.
- The conserved core region of VapA, but not VapD or VapG, mediates these endolysosomal effects.
Conclusions:
- VapA disrupts endolysosomal trafficking and function in macrophages.
- This disruption likely enhances R. equi survival by inhibiting lysosomal clearance of the bacterium.
- This study provides the first mechanistic insight into VapA's role in R. equi pathogenesis.
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