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Journal of Bacteriology, July 2009, p. 4232-4242, Vol. 191, No. 13
0021-9193/09/$08.00+0     doi:10.1128/JB.01656-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The Coxiella burnetii Ankyrin Repeat Domain-Containing Protein Family Is Heterogeneous, with C-Terminal Truncations That Influence Dot/Icm-Mediated Secretion {triangledown}

Daniel E. Voth,1,{dagger} Dale Howe,1 Paul A. Beare,1 Joseph P. Vogel,2 Nathan Unsworth,3 James E. Samuel,3 and Robert A. Heinzen1*

Coxiella Pathogenesis Section, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,1 Department of Molecular Microbiology, Washington University, St. Louis, Missouri 63110,2 Department of Medical Microbiology and Immunology, Texas A&M University System Health Science Center, College Station, Texas 778433

Received 21 November 2008/ Accepted 10 April 2009

Coxiella burnetii is an obligate intracellular bacterium that directs biogenesis of a parasitophorous vacuole (PV) for replication. Effectors of PV maturation are likely translocated into the host cytosol by a type IV secretion system (T4SS) with homology to the Dot/Icm apparatus of Legionella pneumophila. Since secreted bacterial virulence factors often functionally mimic the activities of host proteins, prokaryotic proteins with eukaryotic features are considered candidate T4SS substrates. Genes encoding proteins with eukaryotic-type ankyrin repeat domains (Anks) were identified upon genome sequencing of the C. burnetii Nine Mile reference isolate, which is associated with a case of human acute Q fever. Interestingly, recent genome sequencing of the G and K isolates, derived from human chronic endocarditis patients, and of the Dugway rodent isolate revealed remarkable heterogeneity in the Ank gene family, with the Dugway isolate harboring the largest number of full-length Ank genes. Using L. pneumophila as a surrogate host, we identified 10 Dugway Anks and 1 Ank specific to the G and K endocarditis isolates translocated into the host cytosol in a Dot/Icm-dependent fashion. A 10-amino-acid C-terminal region appeared to be necessary for translocation, with some Anks also requiring the chaperone IcmS for secretion. Ectopically expressed Anks localized to a variety of subcellular regions in mammalian cells, including microtubules, mitochondria, and the PV membrane. Collectively, these data suggest that C. burnetii isolates translocate distinct subsets of the Ank protein family into the host cytosol, where they modulate diverse functions, some of which may be unique to C. burnetii pathotypes.

* Corresponding author. Mailing address: Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, 903 S. 4th Street, Hamilton, MT 59840. Phone: (406) 375-9695. Fax: (406) 363-9380. E-mail: rheinzen{at}niaid.nih.gov

{triangledown} Published ahead of print on 1 May 2009.

{dagger} Present address: Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, AR 72205.

Journal of Bacteriology, July 2009, p. 4232-4242, Vol. 191, No. 13
0021-9193/09/$08.00+0     doi:10.1128/JB.01656-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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