Quinolone resistance from a transferable plasmid
Quinolone resistance from a transferable plasmid
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DOI：
10.1016/s0140-6736(97)07322-4
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发表时间：
1998-03-14
期刊：
影响因子：
168.9
通讯作者：
Jacoby, GA
中科院分区：
文献类型：
--
作者：
Martínez-Martínez, L;Pascual, A;Jacoby, GA
背景细菌可以通过靶点改变或药物蓄积减少而突变获得喹诺酮耐药。质粒介导的喹诺酮类药物耐药已在临床分离，但尚未得到证实。我们研究多重耐药质粒是否可以在细菌之间转移对喹诺酮类药物的耐药性。通过琼脂糖凝胶电泳在不同宿主中观察到抗性质粒。我们测定了大肠杆菌菌株对环丙沙星或萘啶酸耐药性的自发突变频率，结果发现来自肺炎克雷伯氏菌临床分离株的多重耐药质粒（pMG 252）可增加喹诺酮类药物的耐药性，最低抑菌浓度（MIC）高达32 μ g/ml。当转移到缺乏外膜孔蛋白的肺炎克雷伯菌菌株时，环丙沙星的浓度为100 mL。当pMG 252被引入具有正常孔蛋白的肺炎链球菌或大肠杆菌菌株中时，观察到低得多的耐药性。该质粒具有广泛的宿主范围，并在其他肠杆菌科和铜绿假单胞菌中表达喹诺酮耐药。从环丙沙星MIC为0.25 μ g/mL和萘地昔酸MIC为32 μ g/mL的含质粒大肠杆菌菌株中，可以以超过无质粒菌株100倍的频率获得喹诺酮抗性突变体，环丙沙星的MIC为4 μ g/mL，萘啶酸的MIC为256 μ g/mL。在广泛宿主范围质粒上的肺炎衣原体临床分离株中发现了对氟奎宁和萘啶酸的可转移耐药性。尽管野生型菌株的耐药性较低，但突变很容易引起较高水平的喹诺酮类耐药性。这样的质粒可以加速对这些有价值的抗微生物剂的耐药性的发展和传播。
Background Bacteria can mutate to acquire quinolone resistance by target alterations or diminished drug accumulation. Plasmid-mediated resistance to quinolones in clinical isolates has been claimed but not confirmed. We investigated whether a multiresistance plasmid could transfer resistance to quinolones between bacteria.Methods We transferred resistance between strains by conjugation. The resistance plasmid was visualised in different hosts by agarose-gel electrophoresis. We determined the frequency of spontaneous mutations to ciprofloxacin or nalidixic-acid resistance in Escherichia coli strains, with or without the quinolone resistance plasmid.Findings A multiresistance plasmid (pMG252) from a clinical isolate of Klebsiella pneumoniae was found to increase quinolone resistance to minimum inhibitory concentrations (MICs) as high as 32 mu g/mL for ciprofloxacin when transferred to strains of K pneumoniae deficient in outer-membrane porins. Much lower resistance was seen when pMG252 was introduced into It pneumoniae or E coli strains with normal porins. The plasmid had a wide host range and expressed quinolone resistance in other enterobacteriaceae and in Pseudomonas aeruginosa. From a plasmid-containing E coli strain with ciprofloxacin MIC of 0.25 mu g/mL and nalidixic-acid MIC of 32 mu g/mL, quinolone-resistant mutants could be obtained at more than 100 times the frequency of a plasmid-free strain, reaching MICs for ciprofloxacin of 4 mu g/mL and for nalidixic acid of 256 mu g/mL.Interpretation Transferable resistance to fluoroquinines and nalidixic acid has been found in a clinical isolate of It pneumoniae on a broad host range plasmid. Although resistance was low in wild-type strains, higher levels of quinolone resistance arose readily by mutation. Such a plasmid can speed the development and spread of resistance to these valuable antimicrobial agents.