Differential transcription of the MPB7O genes in two major groups of Mycobacterium bovis BCG substrains

Substrains of Mycobacterium bovis BCG (BCG) have been divided into two major groups, high and low producers, on the basis of the amount of secretion of the MPB7O protein. The antigen is produced in high concentration by BCG Tokyo, Moreau, Russia and Sweden (high-producer substrains), whereas in BCG Pasteur, Copenhagen and Tice (low-producer substrains) it is detected at 1% (w/w) or less of the concentration of BCG Tokyo. To investigate why this protein is secreted differently, the MPB7O genes of BCG Tokyo and Pasteur were cloned, sequenced and compared. The MPB7O genes in two substrains showed exactly the same sequence. Even the upstream and downstream regions of the MPB7O gene were identical. MPB7O gene expression was assessed by means of Northern hybridization analysis and reverse transcriptase polymerase chain reaction. The mRNA was clearly detected in BCG Tokyo, but at a very low level in BCG Pasteur. On the basis of these results, the difference in the secretion of the MPB7O protein between BCG Tokyo and Pasteur was attributed to differential transcription efficiencies.