Guillemin I, Jarlier V, Cambau E
Laboratoire de Recherche Moléculaire sur les Antibiotiques, Faculté de Médecine Pitié-Salpêtrière, Université Pierre et Marie Curie (Paris VI), Paris, France.
Antimicrob Agents Chemother. 1998 Aug;42(8):2084-8. doi: 10.1128/AAC.42.8.2084.
The in vitro activities of seven quinolones and the sequences of the quinolone resistance-determining regions (QRDR) in the A and B subunits of DNA gyrase were determined for 14 mycobacterial species. On the basis of quinolone activity, quinolones were arranged from that with the greatest to that with the least activity as follows: sparfloxacin, levofloxacin, ciprofloxacin, ofloxacin, pefloxacin, flumequine, and nalidixic acid. Based on MICs, the species could be organized into three groups: resistant (Mycobacterium avium, M. intracellulare, M. marinum, M. chelonae, M. abscessus [ofloxacin MICs, >/=8 microg/ml]), moderately susceptible (M. tuberculosis, M. bovis BCG, M. kansasii, M. leprae, M. fortuitum third biovariant, M. smegmatis [ofloxacin MICs, 0.5 to 1 microg/ml]), and susceptible (M. fortuitum, M. peregrinum, M. aurum [ofloxacin MICs, </=0.25 microg/ml]). Peptide sequences of the QRDR of GyrB were identical in all the species, including the amino acids at the three positions known to be involved in acquired resistance to quinolone, i.e., 426 (Asp), 447 (Arg), and 464 (Asn) (numbering system used for Escherichia coli). The last two residues could be involved in the overall low level of susceptibility of mycobacteria to quinolones since they differ from those found in the very susceptible E. coli (Lys-447 and Ser-464) but are identical to those found in the less susceptible Staphylococcus aureus and Streptococcus pneumoniae. Peptide sequences of the QRDR of GyrA were identical 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 within the Mycobacterium genus.
测定了7种喹诺酮类药物对14种分枝杆菌的体外活性以及DNA促旋酶A和B亚基中喹诺酮耐药决定区（QRDR）的序列。根据喹诺酮活性，将喹诺酮类药物按活性从高到低排列如下：司帕沙星、左氧氟沙星、环丙沙星、氧氟沙星、培氟沙星、氟甲喹和萘啶酸。根据最低抑菌浓度（MIC），这些菌种可分为三组：耐药组（鸟分枝杆菌、胞内分枝杆菌、海分枝杆菌、龟分枝杆菌、脓肿分枝杆菌[氧氟沙星MIC≥8μg/ml]）、中度敏感组（结核分枝杆菌、牛型结核分枝杆菌卡介苗、堪萨斯分枝杆菌、麻风分枝杆菌、偶然分枝杆菌第三生物变种、耻垢分枝杆菌[氧氟沙星MIC为0.5至1μg/ml]）和敏感组（偶然分枝杆菌、偶发分枝杆菌、金分枝杆菌[氧氟沙星MIC≤0.25μg/ml]）。在所有菌种中，GyrB的QRDR肽序列相同，包括已知与获得性喹诺酮耐药有关的三个位置的氨基酸，即426位（天冬氨酸）、447位（精氨酸）和464位（天冬酰胺）（采用大肠杆菌的编号系统）。最后两个残基可能与分枝杆菌对喹诺酮总体低敏感性有关，因为它们与高度敏感的大肠杆菌中的残基（447位赖氨酸和464位丝氨酸）不同，但与敏感性较低的金黄色葡萄球菌和肺炎链球菌中的残基相同。除了83位氨基酸外，所有菌种中GyrA的QRDR肽序列相同，在两个低敏感组中该氨基酸为丙氨酸，在最敏感组中为丝氨酸，如同在大肠杆菌中一样，这表明该氨基酸与分枝杆菌属内观察到的喹诺酮敏感性差异有关。
