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University of Victoria
ABSTRACT
Several genes contained in the Francisella Pathogenicity Island (FPI) encode proteins needed for intracellular growth and virulence of F. tularensis. The pdpA gene is the first cistron in the larger of the two operons found in the FPI. In this work we studied the intracellular growth phenotype of a F. novicida mutant in the pdpA gene. The
pdpA strain was capable of a small amount of intracellular replication but, unlike wild type F. novicida, remained associated with the lysosomal marker LAMP-1, suggesting PdpA is necessary for progression from the early phagosome phase of infection. Strains with in cis complementation of the
pdpA lesion showed a restoration of intracellular growth to wild type levels. Infection of macrophages with the
pdpA mutant generated a host cell mRNA profile distinct from that generated by infection with wild type F. novicida. The transcriptional response of the host macrophage indicates that PdpA functions directly or indirectly to suppress macrophage ability to signal via growth factors, cytokines, and adhesion ligands.
1 E-mail: fnano{at}uvic.ca
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