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Infection and Immunity, November 2006, p. 6429-6437, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00809-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Structure of the Expression Site Reveals Global Diversity in MSP2 (P44) Variants in Anaplasma phagocytophilum ^,

Anthony F. Barbet,^1* Anna M. Lundgren,¹ A. Rick Alleman,² Snorre Stuen,³ Anneli Bjöersdorff,⁴ Richard N. Brown,⁵ Niki L. Drazenovich,⁶ and Janet E. Foley⁶

Department of Infectious Diseases and Pathology,¹ Department of Physiological Sciences, University of Florida, Gainesville, Florida 32611,² Norwegian School of Veterinary Science, Sandnes N-4325, Norway,³ Department of Clinical Microbiology, Kalmar County Hospital, Kalmar, Sweden,⁴ Department of Wildlife, Humboldt State University, Arcata, California 95521,⁵ Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California 95616⁶

Received 19 May 2006/ Returned for modification 26 June 2006/ Accepted 30 August 2006

Anaplasma phagocytophilum, a recently reclassified bacteria in the order Rickettsiales, infects many different animal species and causes an emerging tick-borne disease of humans. The genome contains a large number of related genes and gene fragments encoding partial or apparently full-length outer membrane protein MSP2 (P44). Previous data using strains isolated from humans in the United States suggest that antigenic diversity results from RecF-mediated conversion of a single MSP2 (P44) expression site by partially homologous donor sequences. However, whether similar mechanisms operate in naturally infected animal species and the extent of global diversity in MSP2 (P44) are unknown. We analyzed the structure and diversity of the MSP2 (P44) expression site in strains derived from the United States and Europe and from infections of different animal species, including wildlife reservoirs. The results show that a syntenic expression site is present in all strains of A. phagocytophilum investigated. This genomic locus contained diverse MSP2 (P44) variants in all infected animals sampled, and variants also differed at different time points during infection. Although similar variants were found among different populations of U.S. origin, there was little sequence identity between U.S. strain variants (including genomic copies from a completely sequenced U.S. strain) and expression site variants infecting sheep and dogs in Norway and Sweden. Finally, the possibility that combinatorial mechanisms can generate additional diversity beyond the basic donor sequence repertoire is supported by the observation of shared sequence blocks throughout the MSP2 (P44) hypervariable region in reservoir hosts. These data suggest similar genetic mechanisms for A. phagocytophilum variation in all hosts but worldwide diversity of the MSP2 (P44) outer membrane protein.

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* Corresponding author. Mailing address: Department of Infectious Diseases and Pathology, College of Veterinary Medicine, Box 110880, Gainesville, FL 32611-0880. Phone: (352) 392-4700, ext. 5819. Fax: (352) 392-9704. E-mail: barbeta{at}mail.vetmed.ufl.edu.

Published ahead of print on 11 September 2006.

Editor: W. A. Petri, Jr.

Supplemental material for this article may be found at http://iai.asm.org/.

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Infection and Immunity, November 2006, p. 6429-6437, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00809-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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