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Journal of Bacteriology, July 2008, p. 4584-4595, Vol. 190, No. 13
0021-9193/08/$08.00+0     doi:10.1128/JB.00198-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Francisella Pathogenicity Island Protein PdpD Is Required for Full Virulence and Associates with Homologues of the Type VI Secretion System{triangledown}

Jagjit S. Ludu,1 Olle M. de Bruin,1 Barry N. Duplantis,1 Crystal L. Schmerk,1 Alicia Y. Chou,2 Karen L. Elkins,2 and Francis E. Nano1*

Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada,1 Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland2

Received 7 February 2008/ Accepted 28 April 2008

Francisella tularensis is a highly infectious, facultative intracellular bacterial pathogen that is the causative agent of tularemia. Nearly a century ago, researchers observed that tularemia was often fatal in North America but almost never fatal in Europe and Asia. The chromosomes of F. tularensis strains carry two identical copies of the Francisella pathogenicity island (FPI), and the FPIs of North America-specific biotypes contain two genes, anmK and pdpD, that are not found in biotypes that are distributed over the entire Northern Hemisphere. In this work, we studied the contribution of anmK and pdpD to virulence by using F. novicida, which is very closely related to F. tularensis but which carries only one copy of the FPI. We showed that anmK and pdpD are necessary for full virulence but not for intracellular growth. This is in sharp contrast to most other FPI genes that have been studied to date, which are required for intracellular growth. We also showed that PdpD is localized to the outer membrane. Further, overexpression of PdpD affects the cellular distribution of FPI-encoded proteins IglA, IglB, and IglC. Finally, deletions of FPI genes encoding proteins that are homologues of known components of type VI secretion systems abolished the altered distribution of IglC and the outer membrane localization of PdpD.

* Corresponding author. Mailing address: Department of Biochemistry and Microbiology, P.O. Box 3055 STN CSC, University of Victoria, Victoria, BC V8W 3P6, Canada. Phone: (250) 721-7074. Fax: (250) 721-8855. E-mail: fnano{at}uvic.ca

{triangledown} Published ahead of print on 9 May 2008.

Journal of Bacteriology, July 2008, p. 4584-4595, Vol. 190, No. 13
0021-9193/08/$08.00+0     doi:10.1128/JB.00198-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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