A historical and molecular phylogeny of BCG strains

Bacillus Calmette-Guerin (BCG) is the name given to a family of vaccines de rived in 1921 by the in-vitro attenuation of Mycobacterium bovis. Subsequen tly, BCG seed lots were distributed globally, and both phenotypic and genot ypic differences between strains have been described. As a step to understa nding BCG diversity, we have reviewed the English and French historical rec ord on 13 strains and DNA was extracted from these strains for restriction- fragment-length-polymorphism study. The written record suggests "early stra ins" obtained from the Pasteur Institute between 1924 and 1926 and "later s trains" obtained after 1931. Molecular typing resulted in 3 clades, based o n variability in IS6110-typing and the presence of mpt64 gene. With two exc eptions, these clades correspond with strains obtained in 1924-26 (IS6110-2 /mpt64+), 1926-31 (IS6110-1/mpt64+), and 1931 or later (IS6110-1/mpt64-) Th is analysis demonstrates that BCG has undergone genetic changes since 1921, consistent with ongoing in-vitro evolution. (C) 1999 Elsevier Science Ltd. All rights reserved.