Molecular basis of rifampin and isonoiazid resistance in Mycobacterium bovis strains isolated in Sardinia, Italy

Fourteen of 22 (68%) Mycobacterium bovis strains isolated from cattle in Sa rdinia were found to be resistant to rifampin and isoniazid, Analysis of th e rpoB and the katG, oxyR-ahpC, and inhA gene regions of these strains was performed in order to investigate the molecular basis of rifampin and isoni azid resistance, respectively. The most frequent mutation, encountered in 6 of 10 strains (60%), was in the rpoB gene; it occurred, at codon position 521 and resulted in leucine changed to proline, This suggests that codon 52 1 may be important for the development of rifampin resistance in M, bovis. Resistance to isoniazid is associated in Mycobacterium tuberculosis with a variety of mutations affecting one or more genes. Our results confirm the d ifficulty of interpreting the sequence variations observed in clinical stra ins of M, bovis. M. bovis strains isolated from the same geographic area sh owed similar mutations within the genes responsible for rifampin and isonia zid resistance. Our results represent the first study to elucidate the mole cular genetic basis of drug resistance in M. bovis isolated from cattle.