Takiff HE, Musso MC, Lopez G, Montero C, Ortiz J, Millan E; American Society for Microbiology. General Meeting.
Abstr Gen Meet Am Soc Microbiol. 1997 May 4-8; 97: 545 (abstract no. U11).
Inst. Venezolano de Investigaciones Cientificas (IVIC), Caracas, Venezuela.
The use of fluoroquinolones (FQ) to treat drug resistant M. tuberculosis, may be limited by the appearance of FQ resistant (FQR) strains. Resistance to the FQ develops in several steps, but their principal targets are the type II topoisomerases, and mutations in a small region of gyrA, encoding the gyrase A subunit, confer clinical resistance to most FQ. Newer FQ, such as DU-6859a, have been reported to be effective against FQR gyrA mutant strains of some species. To evaluate the effectiveness of different FQ against M. tuberculosis, and to study mechanisms of FQ resistance, spontaneous FQR mutants of the closely related M. bovis BCG were selected on low levels of ciprofloxacin (Cipro), ofloxacin (Oflox), levofloxacin (Levo), sparfloxacin (Spar) and DU-6859a. FQR mutants appeared at frequencies of 3 X 10-5 to 1 x 10-7, in drug concentrations ranging from 0.5 micrograms/ml for Ciprofloxacin to 0.062 micrograms/ml for DU-6859-a, in the order Cipro to Oflox to Levo to Spar to DU6859a. Low level FQR strains sequencially restreaked onto higher drug concentrations readily acquired gyrA mutations and were then resistant to at least 4 micrograms/ml of Cipro, Oflox and Levo, and 1 microgram/ml of Spar and DU6859-a. Surprisingly, many low level FQR strains had GyrB mutations further towards the C terminal end than mutations described in E. coli gyrB, but close to mutations described in high level FQR M. tuberculosis strains. Similar gyrA mutations, but not gyrB mutations, were found in FQR strains of M. smegmatis.
Publication Types:
Keywords:
- BCG Vaccine
- Ciprofloxacin
- Fluoroquinolones
- Mutation
- Mycobacterium bovis
- Ofloxacin
- Selection (Genetics)
- Tuberculosis
- genetics
- sitafloxacin
- sparfloxacin
Other ID:
UI: 102235430
From Meeting Abstracts