From 1989 to 1995, 46 patients infected with the human immunodeficiency virus were diagnosed with tuberculosis at the University Hospital in Zurich. Using the IS6110 insertion sequence as a genetic marker, restriction fragment length polymorphism analyses were done for 52 Mycobacterium tuberculosis isolates. We have found a large degree of IS6110 polymorphism, ranging from 1 to 16 copies. For isolates from patients from whom multiple isolates had been available, the IS6110 pattern remained virtually stable over a period of up to 4 years, as well as during emerging drug resistance. In none of the cases was a reinfection of a patient with another strain detected. For isolates from 10 patients we detected identical patterns which could be associated with four clusters. In one of these, the strains exhibited a low IS6110 copy number (four bands), and the strains were further analyzed by hybridizing with (i) the polymorphic GC-rich repetitive sequence (PGRS) and (ii) the 36-bp direct-repeat (DR) cluster sequence. One of these isolates had a different pattern with the PGRS as well as with the DR sequence and could therefore be safely excluded from that cluster. These findings point to the importance of applying more than one genetic criterion in the molecular biological study of strain relatedness.

Teicoplanin resistance was transformed from a teicoplanin-resistant Staphylococcus aureus into the susceptible strain BB255 to give strain BB938. The cell wall composition, amidation of the iD-glutamate, and peptide crosslinking were identical in BB938 as in BB255 except for a 60% increased length of the glycan chain. Transductional crosses revealed that at least two distinct loci contributed in a cumulative fashion to teicoplanin resistance. One of these loci correlated with a mutation inactivating the anti-sigma factor RsbW. This mutation must have occurred during transformation and selection for teicoplanin resistance in BB938. Genetic manipulations involving the sigB operon showed that transcription factor SigB contributed to decreased teicoplanin susceptibility.