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Infection and Immunity, June 2006, p. 3554-3564, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.01950-05

Borrelia burgdorferi OspC Protein Required Exclusively in a Crucial Early Stage of Mammalian Infection

Kit Tilly,^1* Jonathan G. Krum,^1, Aaron Bestor,¹ Mollie W. Jewett,¹ Dorothee Grimm,^1, Dawn Bueschel,^1, Rebecca Byram,^1,¶ David Dorward,² Mark J. VanRaden,³ Philip Stewart,¹ and Patricia Rosa¹

Laboratory of Zoonotic Pathogens, and Research Technologies Section, Microscopy Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840,¹ Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892²

Received 30 November 2005/ Returned for modification 26 January 2006/ Accepted 28 March 2006

This study demonstrates a strict temporal requirement for a virulence determinant of the Lyme disease spirochete Borrelia burgdorferi during a unique point in its natural infection cycle, which alternates between ticks and small mammals. OspC is a major surface protein produced by B. burgdorferi when infected ticks feed but whose synthesis decreases after transmission to a mammalian host. We have previously shown that spirochetes lacking OspC are competent to replicate in and migrate to the salivary glands of the tick vector but do not infect mice. Here we assessed the timing of the requirement for OspC by using an ospC mutant complemented with an unstable copy of the ospC gene and show that B. burgdorferi's requirement for OspC is specific to the mammal and limited to a critical early stage of mammalian infection. By using this unique system, we found that most bacterial reisolates from mice persistently infected with the initially complemented ospC mutant strain no longer carried the wild-type copy of ospC. Such spirochetes were acquired by feeding ticks and migrated to the tick salivary glands during subsequent feeding. Despite normal behavior in ticks, these ospC mutant spirochetes did not infect naive mice. ospC mutant spirochetes from persistently infected mice also failed to infect naive mice by tissue transplantation. We conclude that OspC is indispensable for establishing infection by B. burgdorferi in mammals but is not required at any other point of the mouse-tick infection cycle.

Editor: J. L. Flynn

Present address: College of Eastern Utah—San Juan Campus, Blanding, UT 84511.

Present address: IDEXX Laboratories, Inc., Westbrook, ME 04092.

Present address: Veterinary Diagnostic Services, New Mexico Department of Agriculture, 700 Camino de Salud, NE, Albuquerque, NM 87106.

^¶ Present address: Western Range and Water LLC, 130 S. Main St., P.O. Box 37, Buffalo, WY 82834.

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