Abstract
Rhodococcus equi (R. equi) is an important pulmonary pathogen in foals that often leads to the death of the horse. The bacterium harbors a virulence plasmid that encodes numerous virulence-associated proteins (Vaps) including VapA that is essential for intracellular survival inside macrophages. However, little is known about the precise function of VapA. Here, we demonstrate that VapA causes perturbation to late endocytic organelles with swollen endolysosome organelles having reduced Cathepsin B activity and an accumulation of LBPA, LC3 and Rab7. The data are indicative of a loss of endolysosomal function, which leads cells to upregulate lysosome biogenesis to compensate for the loss of functional endolysosomes. Although there is a high degree of homology of the core region of VapA to other Vap proteins, only the highly conserved core region of VapA, and not VapD of VapG, gives the observed effects on endolysosomes. This is the first demonstration of how VapA works and implies that VapA aids R. equi survival by reducing the impact of lysosomes on phagocytosed bacteria.
| Original language | English |
|---|---|
| Article number | e00416 |
| Number of pages | 17 |
| Journal | Microbiology Open |
| Volume | 6 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 19 Oct 2016 |
Bibliographical note
© 2016 The Authors.Keywords
- Actinomycetales Infections/microbiology
- Animals
- Bacterial Proteins/metabolism
- Base Sequence
- Bronchopneumonia/microbiology
- Cathepsin B/metabolism
- Cell Line, Tumor
- Gene Expression Regulation, Bacterial
- HeLa Cells
- Horse Diseases/microbiology
- Horses
- Humans
- Lysosomes/microbiology
- Macrophages/microbiology
- Phagocytosis
- Rats
- Rhodococcus equi/pathogenicity
- Virulence Factors