Molecular markers demonstrate that the first described multidrug-resistantMycobacterium bovis outbreak was due to Mycobacterium tuberculosis

We genetically characterized multidrug-resistant Mycobacterium tuberculosis complex strains which caused a nosocomial outbreak of tuberculosis affecti ng six human immunodeficiency virus (HIV)-positive patients and one HIV-neg ative staff member (E. Bouvet, E. Casalino, G. Mendoza-Sassi, S. Lariven, E . Vallee, M. Pernet, S. Gottot, and F. Vachon, AIDS 7:1453-1460; 1993), The strains showed all the phenotypic characteristics of Mycobacterium bovis. They presented a high copy number of IS6110, the spacers 40 to 43 in the di rect repeat locus, and the mtp40 fragment. They lacked the G-A mutation at position 285 in the oxyR gene and the C-G mutation at position 169 in the p ncA gene. These genetic characteristics revealed that these were dysgonic, slow-growing M. tuberculosis strains mimicking the M. bovis phenotype, prob ably as a consequence of cellular alterations associated with the multidrug resistance. Spoligotyping and IS6110 restriction fragment length polymorph ism (RFLP) analysis confirmed that the outbreak was due to a single strain. However, the IS6110 RFLP pattern of the strain isolated from the last pati ent, diagnosed three years after the index case, differed slightly from the patterns of the other six strains. A model of a possible genetic event is presented to explain this divergence. This study stresses the value of usin g several independent molecular markers to identify multidrug-resistant tub ercle bacilli.