A Francisella novicida pdpA mutant exhibits limited intracellular replication and remains associated with the lysosomal marker LAMP-1.
Several genes contained in the Francisella pathogenicity island (FPI) encode proteins needed for intracellular growth and virulence of Francisella 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 Francisella novicida mutant in the pdpA gene. The DeltapdpA 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 that PdpA is necessary for progression from the early phagosome phase of infection. Strains with in cis complementation of the DeltapdpA lesion showed a restoration of intracellular growth to wild-type levels. Infection of macrophages with the DeltapdpA 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.
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.
Howard
Perry L
PL
Department of Biology, University of Victoria, Victoria, BC, Canada.|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 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication; D005260:Female; D005603:Francisella / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D015964:Gene Expression Regulation, Bacterial; D016905:Gram-Negative Bacterial Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D006801:Humans; D052118:Lysosomal-Associated Membrane Protein 1 / Q000235:genetics / Q000378:metabolism*; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011485:Protein Binding; D017384:Sequence Deletion; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
D001426:Bacterial Proteins; D052118:Lysosomal-Associated Membrane Protein 1; D037521:Virulence Factors