The actinomycete Rhodococcus equi is a facultative intracellular pathogen, infecting humans, foals and a range of other animals, resulting in pyogranulomatous cavitating pneumonia, ulcerative enteritis and occasionally osteomyelitis and cerebral infections. It is a parasite of macrophages, preventing phagosomal maturation in a process that is dependent on a pathogenicity island (PAI) present on a virulence plasmid. The PAI encodes a family of virulence associated proteins (Vap), one of which is essential for virulence (VapA). We recently solved the structure of these proteins and identified a protein interaction network in which VapA is central. The PAI has a different G+C content than the remainder of the chromosome, suggesting it was most likely acquired by the avirulent ancestor of R. equi via lateral gene transfer. Although the PAI encoded Vap proteins play a critical role in virulence, their presence alone is not sufficient to render an avirulent strain virulent. A genome wide transcriptomic analysis revealed that the presence of the virulence plasmid affects approximately 30% of the transcriptome. We have examined the DNA-protein interaction of a PAI encoded transcriptional regulator with the chromosome, showing that this regulator takes over from chromosomally encoded regulators to dramatically alter gene expression. These data indicate that the emergence of virulence in a non-pathogenic ancestral bacterium was a gradual process that was initiated by the acquisition of a virulence plasmid, followed by alteration of chromosomal gene expression patterns resulting in an adjustment of bacterial physiology to suit the environment of the infected host.
