title: The Rhodococcus equi virulence protein VapA disrupts endolysosome function and stimulates lysosome biogenesis.
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.
authors.affiliation: Department of Biology, Wentworth Way, University of York, York, UK.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Rofe
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge.
authors.forename: Luther J
authors.initials: LJ
authors.lastname: Davis
authors.affiliation: Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Whittingham
authors.affiliation: Cambridge Institute for Medical Research and Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Latimer-Bowman
authors.affiliation: Structural Biology Laboratory, Department of Chemistry, University of York, York, UK.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Wilkinson
authors.affiliation: Department of Biology, Wentworth Way, University of York, York, UK.|Hull York Medical School, University of York, York, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Pryor
mesh_terms: D000193:Actinomycetales Infections / Q000382:microbiology / Q000473:pathology*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D001996:Bronchopneumonia / Q000382:microbiology*; D002401:Cathepsin B / Q000378:metabolism*; D045744:Cell Line, Tumor; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006734:Horse Diseases / Q000382:microbiology / Q000473:pathology*; D006736:Horses; D006801:Humans; D008247:Lysosomes / Q000382:microbiology / Q000473:pathology*; D008264:Macrophages / Q000382:microbiology; D010587:Phagocytosis; D051381:Rats; D016929:Rhodococcus equi / Q000472:pathogenicity*; D037521:Virulence Factors
chemical_list: D001426:Bacterial Proteins; C541879:VapA protein, Rhodococcus equi; D037521:Virulence Factors; D002401:Cathepsin B
keywords: 
  Rhodococcus equi
  ; VapA; endolysosome; lysosome