Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicida

Abstract
Francisella tularensisis a highly virulent, intracellular pathogen that causes the disease tularaemia. A research surrogate forF. tularensisisFrancisella novicida, which causes a tularaemia-like disease in mice, grows similarly in macrophages, and yet is unable to cause disease in humans. BothFrancisellaspecies contain a cluster of genes referred to as theFrancisellapathogenicity island (FPI). Pathogenicity determinant protein A (PdpA), encoded by thepdpAgene, is located within the FPI and has been associated with the virulence ofFrancisellaspecies. In this work we examined the properties of PdpA protein expression and localization as well as the phenotype of aF. novicida pdpAdeletion mutant. Monoclonal antibody detection of PdpA showed that it is a soluble protein that is upregulated in iron-limiting conditions and undetectable in anmglAormglBmutant background. Deletion ofpdpAresulted in a strain that was highly attenuated for virulence in chicken embryos and mice.