Molecular Phylogeny of the Mycobacterium avium Complex Demonstrates Clinically Meaningful Divisions

Abstract

Phylogenetic analysis of nucleotide sequence data is widely used for viral epidemiology. To explore its use in bacterial strain differentiation, the variable 16S-23S rDNA internal transcribed spacer (ITS) in 24 clinical isolates originally identified as Mycobacterium avium complex (MAC) was sequenced. Three isolates had an identical sequence that differed greatly from the rest. They belonged to the recently described Mycobacterium celatum. The 21 MAC clinical isolates gave 6 ITS sequences, each defining a sequevar. Thirteen isolates from 11 AIDS patients with disseminated MAC disease belonged to 2 sequevars, which differed in ITS sequence by 1 nucleotide. In contrast, 7 pulmonary-source MAC isolates were genetically more diverse. They belonged to 4 sequevars, which differed from each other by 6-20 nucleotides and from the disseminated disease-associated sequevars by at least 12 nucleotides. The single urine MAC isolate had the same sequence as 1 of the pulmonary isolates. Because the disseminated disease-associated MAC strains were distinct by ITS sequence analysis, it should be possible to develop a molecular assay to detect them directly in clinical specimens or in environmental samples. Molecular phylogeny at the strain level may be widely useful in studies of bacterial epidemiology and virulence.