Hooper D C, Wolfson J S, Souza K S, Tung C, McHugh G L, Swartz M N
Antimicrob Agents Chemother. 1986 Apr;29(4):639-44. doi: 10.1128/AAC.29.4.639.
In Escherichia coli the frequency of spontaneous single-step mutation to high levels of resistance to the newer 4-quinolone agent norfloxacin was confirmed to be over 300-fold lower than that to the older agent nalidixic acid. Serial passage on incremental concentrations of drug was necessary to produce mutants highly resistant to norfloxacin. Genetic analysis of one such highly resistant strain identified two mutations conferring drug resistance. One mutation, nfxA, mapped around 48 min on the E. coli genetic map and was shown to be an allele of gyrA by studies demonstrating an increased drug resistance of DNA gyrase reconstituted with the gyrase A subunit isolated from the mutant strain. These findings also identified the DNA gyrase A subunit as a target of norfloxacin. The second mutation, nfxB, mapped between 20 and 22 min was associated with additional resistances to tetracycline, chloramphenicol, and cefoxitin and with decreases in outer membrane porin protein OmpF. The nfxA and nfxB mutations together accounted for most, but not all, of the norfloxacin resistance phenotype of this strain.
在大肠杆菌中，自发单步突变为对新型4-喹诺酮类药物诺氟沙星产生高水平抗性的频率，经证实比突变为对旧药萘啶酸产生抗性的频率低300倍以上。必须在递增浓度的药物上连续传代，才能产生对诺氟沙星高度耐药的突变体。对其中一个高度耐药菌株进行遗传分析，鉴定出两个赋予耐药性的突变。一个突变，nfxA，定位于大肠杆菌遗传图谱上约48分钟处，通过研究表明，用从突变菌株分离的gyrase A亚基重建的DNA促旋酶的耐药性增加，从而证明它是gyrA的一个等位基因。这些发现还确定了DNA促旋酶A亚基是诺氟沙星的一个靶点。第二个突变，nfxB，定位于20至22分钟之间，与对四环素、氯霉素和头孢西丁的额外抗性以及外膜孔蛋白OmpF的减少有关。nfxA和nfxB突变共同构成了该菌株诺氟沙星耐药表型的大部分，但不是全部。
