Courtright J B, Turowski D A, Sonstein S A
Department of Biology, Marquette University, Milwaukee, WI 53233.
J Antimicrob Chemother. 1988 Feb;21 Suppl B:1-18. doi: 10.1093/jac/21.suppl_b.1.
Enoxacin inhibits growth of Escherichia coli K12 strains primarily by binding to the GyrA subunit of DNA gyrase (topoisomerase II); strains with gyrA, but not gyrB, mutations are less susceptible to the bactericidal effects of this agent. In sensitive strains, enoxacin completely inhibits DNA synthesis within 5 min and produces drug-gyrase-DNA complexes at numerous sites throughout the E. coli chromosome, as shown by the formation of linear DNA molecules after detergent treatment. Enoxacin, even at subminimal inhibitory concentrations, induces the bacterial SOS system, even in partially resistant gyrA strains. This drug also inhibits the induced expression of the lacZ encoded beta-galactosidase, regardless of whether this gene is located on the chromosome, a low copy number F' plasmid or high copy number Col E1 related plasmids. This inhibition of gene expression at subminimal inhibitory concentrations is likely to be a factor, in addition to gyrase inhibition, in the elimination of Col E1 plasmids and to the reduction in R plasmid conjugal transfer. Enoxacin enhances the bactericidal effects of kanamycin in both in-vitro and in-vivo models, suggesting that this quinolone may be effective in the treatment of infections due to strains resistant to antibacterials as a consequence of plasmid encoded resistance determinants.
依诺沙星主要通过与DNA回旋酶（拓扑异构酶II）的GyrA亚基结合来抑制大肠杆菌K12菌株的生长；携带gyrA而非gyrB突变的菌株对该药物的杀菌作用敏感性较低。在敏感菌株中，依诺沙星在5分钟内可完全抑制DNA合成，并在大肠杆菌整个染色体的多个位点产生药物 - 回旋酶 - DNA复合物，去污剂处理后线性DNA分子的形成即表明了这一点。即使在亚最小抑菌浓度下，依诺沙星也会诱导细菌的SOS系统，即使在部分耐药的gyrA菌株中也是如此。该药物还会抑制由lacZ编码的β-半乳糖苷酶的诱导表达，无论该基因是位于染色体上、低拷贝数的F'质粒上还是高拷贝数的Col E1相关质粒上。除了抑制回旋酶外，亚最小抑菌浓度下对基因表达的这种抑制作用可能是导致Col E1质粒消除以及R质粒接合转移减少的一个因素。依诺沙星在体外和体内模型中均增强了卡那霉素的杀菌作用，这表明这种喹诺酮类药物可能对治疗因质粒编码的耐药决定因素而对抗菌药物耐药的菌株引起的感染有效。
