Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicida.
Francisella tularensis is a highly virulent, intracellular pathogen that causes the disease tularaemia. A research surrogate for F. tularensis is Francisella novicida, which causes a tularaemia-like disease in mice, grows similarly in macrophages, and yet is unable to cause disease in humans. Both Francisella species contain a cluster of genes referred to as the Francisella pathogenicity island (FPI). Pathogenicity determinant protein A (PdpA), encoded by the pdpA gene, is located within the FPI and has been associated with the virulence of Francisella species. In this work we examined the properties of PdpA protein expression and localization as well as the phenotype of a F. novicida pdpA deletion mutant. Monoclonal antibody detection of PdpA showed that it is a soluble protein that is upregulated in iron-limiting conditions and undetectable in an mglA or mglB mutant background. Deletion of pdpA resulted in a strain that was highly attenuated for virulence in chicken embryos and mice.
Schmerk
Crystal L
CL
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Duplantis
Barry N
BN
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Wang
Diana
D
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Burke
Robert D
RD
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Chou
Alicia Y
AY
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.
Elkins
Karen L
KL
Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.
Ludu
Jagjit S
JS
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Nano
Francis E
FE
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002642:Chick Embryo; D005603:Francisella / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D044404:Genomic Islands; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012995:Solubility; D014774:Virulence; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D001426:Bacterial Proteins; D037521:Virulence Factors; D007501:Iron