Characterization by automated DNA sequencing of mutations in the gene (rpoB) encoding the RNA polymerase VOL

Automated DNA sequencing was used to characterize mutations associated with rifampin resistance in a 69-bp region of the gene, rpoB, encoding the P subunit of RNA polymerase in Mycobacterium tuberculosis. The data confirmed that greater than 90 % of rifampin-resistant strains have sequence alterations in this region and showed that most are missense mutations. The analysis also identified several mutant rpoB alleles not previously associated with resistant organisms and one short region of rpoB that had an unusually high frequency of insertions and deletions. Although many strains with an identical IS6110 restriction fragment length polymorphism pattern have the same variant rpoB allele, some do not, a result that suggests the occurrence of evolutionary divergence at the clone level. Tuberculosis, a disease whose frequency declined steadily in the United States since the early 1950s, has resurged, although it was optimistically thought that it might be virtually elimi-nated by the end of the first decade of the 21st century (2). The yearly decline in tuberculosis incidence ended in 1984, and after several years of a plateau phase, the incidence increased from 1988 through 1992 (13). An estimated 51,700 exces