Mutation rate and evolution of fluoroquinolone resistance in Escherichia coli isolates from patients with urinary tract infections
Mutation rate and evolution of fluoroquinolone resistance in Escherichia coli isolates from patients with urinary tract infections
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DOI：
10.1128/aac.47.10.3222-3232.2003
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发表时间：
2003-10-01
影响因子：
4.9
通讯作者：
Hughes, D
中科院分区：
文献类型：
--
作者：
Lindgren, PK;Karlsson, Å;Hughes, D
对来自无并发症尿路感染患者的大肠杆菌菌株进行DNA测序，检测六种基因的氟喹诺酮类药物耐药相关突变：gyrA、gyrB、parC、parE、marOR和acrR。54株菌株的药敏范围分布在15种氟喹诺酮类药物的稀释度上。氟喹诺酮类药物的MIC与菌株携带的耐药突变数量之间存在相关性，耐药菌株在这些基因中有两到五个发生突变。大多数耐药菌株携带两个gyrA突变和一个parC突变。此外，许多耐药菌株具有parE、marOR和/或acrR突变。gyrB未发现耐药突变。因此，氟喹诺酮类药物耐药性的演变涉及多个基因的多重突变的积累。这些临床菌株的自发突变率相差2个数量级。高突变率与临床耐药表型密切相关。这种相关性表明，一般突变率的增加可能通过增加罕见新突变的积累速度，在氟喹诺酮类药物的高水平耐药性的发展中发挥重要作用。
Escherichia coli strains from patients with uncomplicated urinary tract infections were examined by DNA sequencing for fluoroquinolone resistance-associated mutations in six genes: gyrA, gyrB, parC, parE, marOR, and acrR. The 54 strains analyzed had a susceptibility range distributed across 15 dilutions of the fluoroquinolone MICs. There was a correlation between the fluoroquinolone MIC and the number of resistance mutations that a strain carried, with resistant strains having mutations in two to five of these genes. Most resistant strains carried two mutations in gyrA and one mutation in parC. In addition, many resistant strains had mutations in parE, marOR, and/or acrR. No (resistance) mutation was found in gyrB. Thus, the evolution of fluoroquinolone resistance involves the accumulation of multiple mutations in several genes. The spontaneous mutation rate in these clinical strains varied by 2 orders of magnitude. A high mutation rate correlated strongly with a clinical resistance phenotype. This correlation suggests that an increased general mutation rate may play a significant role in the development of high-level resistance to fluoroquinolones by increasing the rate of accumulation of rare new mutations.