The role of bacterial virulence factors in a newly defined model of murine pneumonic yersiniosis

The gram negative bacterium Yersinia causes various diseases in animals and humans. Y. pseudotuberculosis and Y. enterocolitica are transmitted by the fecal-oral route, and cause self-limiting gastroenteritis and lymphadenitis. Y. pestis , causes bubonic and pneumonic plague, and is responsible for three major pandemics, including the Black Death. Y. pestis is believed to have evolved from Y. pseudotuberculosis less than 20,000 years ago, while Y. enterocolitica is more distantly related. All three pathogenic Yersinia harbor a 70Kb virulence plasmid, pYV, which encodes a type three secretion system (TTSS) as well as 5-6 translocated effector proteins, called Yops. Due to its genetic similarity to Y. pestis, the ability of a serotype III strain of Y. pseudotuberculosis, IP2666, to cause pneumonic disease in mice was determined. Mice intranasally inoculated with low doses of Y. pseudotuberculosis developed fulminant infection histologically consistent with pneumonia, which was dependent on a functional TTSS, YopH, and the PhoP/Q two-component regulatory system. Pneumonic models for enteric pathogens such as Shigella, Vibrio, and Campylobacter exist; however, Y. pseudotuberculosis behaved more similarly to known pneumonic pathogens in the model presented here. Colonization of the lungs was robust and bacterial burdens increased over the course of infection. Furthermore, lung colonization was not mouse strain specific. Systemic organs, such as livers and spleens, of mice were not colonized efficiently by the IP2666 strain, but were colonized to high levels by the serotype 1b strain, IP32953. Using IP32953, the roles of adherence factors in bacterial dissemination to the spleen and liver were examined. Specifically, the activity of the adhesins YadA and the pH 6 antigen were investigated in the IP2666 and IP32953 strains. IP32953 DeltayadA and pH 6 Ag- strains were deficient in colonizing the spleen following intranasal inoculation. Strikingly, IP32953 DeltayadA translocated Yops into a different spectrum of host cells than IP32953, suggesting a role for YadA in targeting specific host cell populations for translocation of Yops.