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Infection and Immunity, September 2005, p. 5603-5611, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5603-5611.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Experimental Infection Model for Johne's Disease in Sheep

D. J. Begg,1 R. O'Brien,1 C. G. Mackintosh,2 and J. F. T. Griffin1*

Disease Research Laboratory, Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand,1 AgResearch Invermay, Mosgiel, New Zealand2

Received 13 December 2004/ Returned for modification 29 January 2005/ Accepted 18 April 2005

Johne's disease in ruminants results in chronic enteritis caused by the pathogenic bacterium Mycobacterium avium subsp. paratuberculosis. This study examined two M. avium subsp. paratuberculosis strains (JD3 and W), using different doses and routes of infection, to establish the optimal time postchallenge when predictable levels of infection, gut lesions, and clinical disease occur in a large proportion of sheep. While a small proportion (25%) of sheep challenged with a low-passage-number laboratory culture of M. avium subsp. paratuberculosis (strain W) became infected, no infection was found in animals exposed to a high-passage-number culture isolate of strain W. In contrast, a primary tissue homogenate of M. avium subsp. paratuberculosis (JD3) resulted in high (90%) infection rates and gut histopathology following oral or intratonsillar challenge. The optimal conditions necessary to produce Johne's disease involve oral inoculation of 3-month-old lambs with four doses of 5 x 108 CFU of M. avium subsp. paratuberculosis isolated directly from the gut lymphatic tissues of clinically affected sheep. This resulted in consistent gut histopathology at 9 months and the onset of clinical disease by 11 months postchallenge.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Otago, P. O. Box 56, Dunedin, New Zealand. Phone: 64 3 4797710. Fax: 64 3 4772160. E-mail: frank.griffin{at}stonebow.otago.ac.nz.

Editor: J. L. Flynn

Infection and Immunity, September 2005, p. 5603-5611, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5603-5611.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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