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.
Highlights
Rhodococcus equi, (R. equi) is a Gram-positive facultative intracellular pathogen with similarities to Mycobacterium tuberculosis (Vazquez-Boland et al, 2013)
Given that R.equi has no known secretory system for translocating effector proteins into the host cell cytoplasm (Letek et al, 2010) we considered the possibility that VapA may aid R.equi survival from within the R.equi-containing vacuole (RCV)
HeLa cells, J774.2 mouse macrophages and Normal Rat Kidney (NRK) cells were incubated with 100 μg/ml tagged-VapA, to allow VapA to be taken up by fluid-phase endocytosis
Summary
Rhodococcus equi, (R. equi) is a Gram-positive facultative intracellular pathogen with similarities to Mycobacterium tuberculosis (Vazquez-Boland et al, 2013). Current treatments for R. equi infections involve combination drug therapies with rifampin and macrolides such as clarithromycin (Giguère et al, 2011). These treatments can be protracted and expensive, and are not always successful. While promising potential vaccines are in development, there are still no commercially-available vaccines (Cauchard S et al, 2013) and research efforts are focussing on the mechanisms of pathogenicity induced by R. equi in order to provide insights which may lead to better treatments for infection
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