Stability of Mycobacterium tuberculosis IS6110 restriction fragment lengthpolymorphism patterns and spoligotypes determined by analyzing serial isolates from patients with drug-resistant tuberculosis

The stability of Mycobacterium tuberculosis IS6110 fingerprint patterns and spoligotypes has been assessed by analyzing serial isolates from patients with drug-resistant tuberculosis. Altogether, 165 M. tuberculosis isolates obtained from 56 patients have been analyzed. The time spans between the fi rst and the last or a changed isolate from one patient ranged from 1 to 772 days. Among the 56 patients, 5 (9%) were infected with isolates with chang es in their IS6110 fingerprint patterns. According to the total number of s trains analyzed, 5% of the subsequent isolates showed variations in their I S6110 restriction fragment length polymorphism patterns compared to the pat tern of the first isolates. Up to 10 Isolates from one patient sampled at t ime intervals of up to 772 days with no changes in their IS6110 patterns ha ve been analyzed. A statistically significant correlation could be found be tween changes in insertion sequence (IS) patterns and the increased time in tervals over which the isolates were obtained, whereas changes in IS patter ns are not correlated to changes in the drug resistance of the isolates. In contrast to the observed variations in IS6110 fingerprint patterns, no cha nges in the spoligotypes of the isolates analyzed could be found. In conclu sion, our results confirm that the IS6110 fingerprint patterns of M. tuberc ulosis isolates have high degrees of stability. Compared to IS6110, the dir ect repeat (DR) region, which is the basis for spoligotyping, has a lower r ate of change. Partial deletions, e.g., deletions induced by homologous rec ombination between the repetitive DR elements, could not be detected in thi s study.