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Research Abstracts Online
January 2010 - March 2011

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University of Minnesota Twin Cities
College of Veterinary Medicine
Department of Veterinary Population Medicine

PI: Srinand Sreevatsan, Associate Fellow

Pathogenomics of Infectious Diseases

Mycobacterium bovis Bacille Calmette Guerin (BCG) is the primary vaccine used for tuberculosis (TB) in humans. While BCG elicits an immune response that may or may not correlate with protection, it is rarely associated with disease except in HIV-positive patients in Africa. It is generally accepted that the attenuating defect of BCG is due to RD-1 deletion that contains genes encoding ESAT-6, CFP-10, and several associated proteins shown to be critical in TB pathogenesis. Recently, these researchers have determined that the Ravenel strain of M. bovis is attenuated in cattle. Aerosol exposure of cattle to M. bovis Ravenel results in robust cellular immune responses without disease as has been established with Mycobacterium tuberculosis H37RV infection of cattle. Experimental M. bovis Ravenel challenge of mice, however, results in severe disease (exceeding that of field strains of M. tuberculosis). Sequence analysis indicates that M. bovis Ravenel is nearly identical to the virulent M. bovis, and M. bovis Ravenel carries an intact RD-1 region. One hypothesis is that the observed attenuation may be due to cell wall lipid modulation—this, however, does not explain its enhanced virulence in mice. In as much as the primary reasons of attenuation of Ravenel differ from BCG, and M. tuberculosis appears to be attenuated in cattle, these researchers are testing the hypothesis that understanding the mechanisms of attenuation of MTBC strains in cattle will provide definition of virulence determinants not detected via comparative genomics. By defining defects of attenuation beyond RD-1 deletion, the researchers hope to determine intervention strategies for this costly disease of cattle and humans.

Group Members

Ramakrishnan Muthannan Andavar, Research Associate
Shin Enomoto, Research Associate
Preethi Haran, Graduate Student
Lance G. Hellstrom, Graduate Student
Harish K. Janagama, Graduate Student
Abirami Kugadas, Graduate Student
Elise Lamont, Graduate Student
Amanda Oliveira, Graduate Student
Kamol Suwannakarn, Graduate Student
Ping Wang, Staff
My Yang, Staff