CORRELATION BETWEEN QUINOLONE SUSCEPTIBILITY PATTERNS AND SEQUENCES IN THE A-SUBUNITS AND B-SUBUNITS OF DNA GYRASE IN MYCOBACTERIA

The in vitro activities of seven quinolones and the sequences of the q uinolone resistance determining regions (QRDR) in the A and B subunits of DNA gyrase were determined for 14 mycobacterial species, On the ba sis of quinolone activity, quinolones were arranged from that with the greatest to that with the least activity as follows: sparfloxacin, le vofloxacin, ciprofloxacin, ofloxacin, pefloxacin, flumequine, and nali dixic acid. Based on MICs, the species could be organized into three g roups: resistant (Mycobacterium avium, M. intracellulare, M. marinum, M. chelonae, M. abscessus [ofloxacin MICs, greater than or equal to 8 mu g/ml]), moderately susceptible (M. tuberculosis, M. bovis BCG, M. k ansasii, M. leprae, M. fortuitum third biovariant, M. smegmatis [oflox acin MICs, 0.5 to 1 mu g/ml]), and susceptible (M. fortuitum, M. pereg rinum, M. aurum [ofloxacin MICs, less than or equal to 0.25 mu g/ml]). Peptide sequences of the QRDR of GyrB were identical in all the speci es, including the amino acids at the three positions known to be invol ved in acquired resistance to quinolone, i.e,, 426 (Asp), 447 (Arg), a nd 464 (Asn) (numbering system used for Escherichia coli), The last tw o residues could be involved in the overall low level of susceptibilit y of mycobacteria to quinolones since they differ from those found in the very susceptible E. coli (Lys-447 and Ser-464) but are identical t o those found in the less susceptible Staphylococcus aureus and Strept ococcus pneumoniae. Peptide sequences of the QRDR of GyrA were identic al in all the species, except for the amino acid at position 83, which was an alanine in the two less susceptible groups and a serine in the most susceptible one, as in E. coli, suggesting that this amino acid is involved in the observed differences of quinolone susceptibility wi thin the Mycobacterium genus.