Emergence of multidrug-resistant mutants is increased under antibiotic selective pressure in Pseudomonas aeruginosa

Emergence of multidrug-resistant mutants is increased under antibiotic selective pressure in Pseudomonas aeruginosa
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DOI:
10.1099/00221287-145-10-2857
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发表时间:
1999-10-01
期刊:
影响因子:
2.8
通讯作者:
Martínez, JL
Martínez, JL
中科院分区:
生物学4区
文献类型:
--
作者:
Alonso, A;Campanario, E;Martínez, JL

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铜绿假单胞菌是包括囊性纤维化患者在内的医院感染的重要条件致病菌之一。由于持续的抗生素选择压力,医院分离株经常出现多药耐药(MDR)表型。抗生素选择压力下铜绿假单胞菌多药耐药突变株的产生动力学表明,在抑菌抗生素四环素的存在下,长期孵育使铜绿假单胞菌PAO1的单位细胞日突变率增加了几个数量级。获得的四环素抗性突变株稳定,对不同结构家族抗生素的敏感性降低,并且含有野生型铜绿假单胞菌PAO1所没有的外膜蛋白。这些数据与这样的假设相一致,即在四环素存在的情况下孵育有利于铜绿假单胞菌出现多药耐药突变。这些结果对于理解细菌群体在感染过程中迅速出现耐药突变是相关的。从适应性突变现象的角度,讨论了它们与其他在应激状态下增加突变的模型的关系。
Pseudomonas aeruginosa is one of the most important opportunistic pathogens involved in nosocomial infections, cystic fibrosis patients included. Hospital isolates frequently present multidrug-resistance (MDR) phenotypes as the consequence of constant antibiotic selective pressure. The kinetics of emergence of P. aeruginosa MDR mutants under antibiotic selective pressure indicated that long-term incubation in the presence of the bacteriostatic antibiotic tetracycline increases the mutation rate per cell per day of P. aeruginosa PAO1 by several orders of magnitude. The tetracycline-resistant mutants obtained were stable, showed decreased susceptibility to antibiotics belonging to different structural families, and contained an outer-membrane protein not present in the wild-type P. aeruginosa strain PAO1. These data are consistent with the hypothesis that incubation in the presence of tetracycline favours the emergence of MDR mutants in P. aeruginosa. The results are relevant for understanding the rapid emergence of antibiotic-resistant mutants among bacterial populations during infections. Their relationship to other models of increased mutagenesis under stress is discussed with respect to the adaptive mutation phenomenon.