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Microbiology 155 (2009), 1498-1504; DOI  10.1099/mic.0.025445-0
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Microbiology 155 (2009), 1498-1504; DOI  10.1099/mic.0.025445-0
© 2009 Society for General Microbiology

A Francisella novicida pdpA mutant exhibits limited intracellular replication and remains associated with the lysosomal marker LAMP-1

Crystal L. Schmerk1, Barry N. Duplantis1, Perry L. Howard1,2 and Francis E. Nano1

1 Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada
2 Department of Biology, University of Victoria, Victoria, BC, Canada

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 {Delta}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 that PdpA is necessary for progression from the early phagosome phase of infection. Strains with in cis complementation of the {Delta}pdpA lesion showed a restoration of intracellular growth to wild-type levels. Infection of macrophages with the {Delta}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.

Correspondence
Francis E. Nano
fnano{at}uvic.ca

Abbreviations: BMDM, bone-marrow-derived macrophages; FPI, Francisella pathogenicity island; T6SS, type VI secretion system

Three supplementary tables are available with the online version of this paper.




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C. L. Schmerk, B. N. Duplantis, D. Wang, R. D. Burke, A. Y. Chou, K. L. Elkins, J. S. Ludu, and F. E. Nano
Characterization of the pathogenicity island protein PdpA and its role in the virulence of Francisella novicida
Microbiology, May 1, 2009; 155(5): 1489 - 1497.
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