DEMONSTRATION OF ACQUIRED-RESISTANCE IN BCGR INBRED MOUSE STRAINS INFECTED WITH A LOW-DOSE OF BCG MONTREAL

Abstract

The relationship between natural resistance to Mycobacterium bovis BCG, expressed by the Bcg gene, and the generation of acquired resistance to this infection in various selected inbred strains of mice was investigated. Consistent with previous findings, a low dose (.apprx. 104) of BCG Montreal grew progressively in the spleens of inbred mouse strains previously designated susceptible to BCG (Bcgs), but grew poorly in resistant strains (Bcgr). In contrast, little difference was observed in the growth of the organism in the liver or lungs of these mice, whereas all animals behaved as Bcgs when infected with the World Standard preparation of BCG, BCG Pasteur. Four strains tested (Bcgr; A/J, C3H/HeJ and Bcgs; B10,A/J, BALB/c) all showed evidence of the generation of acquired resistance to a small inoculum of BCG Montreal, as demonstrated by their substantial protection against a subsequent i.v. challenge with virulent M. tuberculosis. These findings are interpreted as being inconsistent with the Bcg gene hypothesis and call into doubt the usage of the term Bcg as a gene designation.