Mutations responsible for reduced susceptibility to 4-quinolones in clinical isolates of multi-resistant Salmonella typhi in India

Mutations responsible for reduced susceptibility to 4-quinolones in clinical isolates of multi-resistant Salmonella typhi in India
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DOI:
10.1093/jac/37.5.891
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发表时间:
1996-05-01
影响因子:
5.2
通讯作者:
Amyes, SGB
Amyes, SGB
中科院分区:
医学2区
文献类型:
--
作者:
Brown, JC;Shanahan, PMA;Amyes, SGB

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在印度Vellore分离的12株伤寒沙门氏菌对4-喹诺酮类药物(环丙沙星的MIG为0.256 mg/L)的敏感性降低。1株分离于1992年,其余11株分离于1994年。采用聚合酶链式反应扩增gyrA基因密码子24 ~ 185段,包括“喹诺酮耐药决定区”,分离扩增链后直接测序。在1992年的一个分离株中,与环丙沙星敏感的分离株相比,gyrA的这一区域未见变化,可能是由于细胞外膜通透性降低或其他机制导致4-喹诺酮类药物敏感性降低。在1994年的9株分离株中,GyrA位点83位的丝氨酸被苯丙氨酸取代与4-喹诺酮类药物敏感性降低相关。在其余两个分离株中,在87号位置发现了新的天冬氨酸取代酪氨酸;在一个分离物中,这个取代与另一个取代在83位偶联,而在另一个分离物中则没有。
Twelve isolates of Salmonella typhi isolated in Vellore, India had reduced susceptibility to 4-quinolones (MIG of ciprofloxacin 0.256 mg/L). One isolate was isolated in 1992 but the remaining 11 were isolated in 1994. The section of the gyrA gene from codons 24 to 185, which includes the ''Quinolone Resistance Determining Region'', was amplified by the polymerase chain reaction and, after separating the amplified strands, the DNA was sequenced directly. In the one isolate from 1992, no alterations were seen in this region of gyrA, compared with the ciprofloxacin-sensitive isolates and presumably decreased 4-quinolone susceptibility resulted from reduced permeability of the cell outer membrane or another mechanism. In nine isolates from 1994, a substitution of phenylalanine for serine at position 83 of GyrA correlated with the decrease in 4-quinolone susceptibility. In the remaining two isolates, the novel substitution of aspartate to tyrosine at position 87 was found; in one isolate this substitution was coupled with another substitution at position 83 but in the other it was not.