Robillard N J
Pharmaceutical Division, Miles Inc., West Haven, Connecticut 06516.
Antimicrob Agents Chemother. 1990 Oct;34(10):1889-94. doi: 10.1128/AAC.34.10.1889.
The Escherichia coli gyrase A gene was cloned in the broad-host-range cosmid vector pLA2917. The resulting plasmid, pNJR3-2, conferred quinolone susceptibility on a gyrA mutant of E. coli. To analyze the expression of this E. coli gene in Pseudomonas aeruginosa, pNJR3-2 or pLA2917 was mobilized via conjugation into P. aeruginosa PAO2 and several well-characterized quinolone-resistant mutants of this strain. The vector pLA2917 did not significantly affect the quinolone susceptibilities of any of the P. aeruginosa strains. However, pNJR3-2 conferred wild-type quinolone susceptibility on P. aeruginosa cfxA (gyrA) mutants and intermediate quinolone susceptibility on cfxA-cfxB double mutants of P. aeruginosa. The quinolone susceptibility of P. aeruginosa PAO2 gyrA+ was unaffected by pNJR3-2. Also, pNJR3-2 had no significant effect on P. aeruginosa cfxB (permeability) mutants. These results demonstrate that the DNA gyrase A gene from E. coli is expressed in P. aeruginosa and confers dominant susceptibility on gyrA mutants. Thus, pNJR3-2 can be used to detect the quinolone resistance mutations that occur in the gyrase A gene of this organism. pNJR3-2 also appears to discriminate between mutations in gyrA and mutations which alter permeability. This gyrase A probe was used successfully in the analysis of quinolone resistance in clinical isolates of P. aeruginosa.
将大肠杆菌的促旋酶A基因克隆到广宿主范围的黏粒载体pLA2917中。所得质粒pNJR3 - 2赋予大肠杆菌的一个促旋酶A突变体对喹诺酮类药物的敏感性。为了分析该大肠杆菌基因在铜绿假单胞菌中的表达情况,通过接合作用将pNJR3 - 2或pLA2917导入铜绿假单胞菌PAO2及其几个特征明确的喹诺酮耐药突变株中。载体pLA2917对任何铜绿假单胞菌菌株的喹诺酮敏感性均无显著影响。然而,pNJR3 - 2赋予铜绿假单胞菌cfxA(促旋酶A)突变体野生型喹诺酮敏感性,并赋予铜绿假单胞菌cfxA - cfxB双突变体中等程度的喹诺酮敏感性。pNJR3 - 2对铜绿假单胞菌PAO2 gyrA +的喹诺酮敏感性没有影响。此外,pNJR3 - 2对铜绿假单胞菌cfxB(通透性)突变体也没有显著影响。这些结果表明,来自大肠杆菌的DNA促旋酶A基因在铜绿假单胞菌中表达,并赋予促旋酶A突变体显性敏感性。因此,pNJR3 - 2可用于检测该生物体促旋酶A基因中发生的喹诺酮耐药突变。pNJR3 - 2似乎也能区分促旋酶A中的突变和改变通透性的突变。这种促旋酶A探针已成功用于分析铜绿假单胞菌临床分离株中的喹诺酮耐药性。