Mutations in topoisomerase genes of fluoroquinolone-resistant salmonellae in Hong Kong
Mutations in topoisomerase genes of fluoroquinolone-resistant salmonellae in Hong Kong
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DOI：
10.1128/aac.47.11.3567-3573.2003
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发表时间：
2003-11-01
影响因子：
4.9
通讯作者：
Cheng, AF
中科院分区：
文献类型：
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作者：
Ling, JM;Chan, EW;Cheng, AF
采用多重聚合酶链式反应方法对88株沙门氏菌(72株环丙沙星MIC<0.06mug/ml，15株环丙沙星MIC<0.06mug/ml，以及肠炎沙门氏菌ATCC 13311)的gyrA、gyrB、parc和pare四种喹诺酮类耐药基因进行了研究。通过核苷酸直接测序证实了这些基因的改变。相当多的菌株在PARC中发生了突变，这是沙门氏菌中首次报告的突变。在对每毫升0.06杯环丙沙星敏感的菌株中，有7株在ParC 57密码子(Tyr57-->；Ser)有新的突变，在29株环丙沙星MIC为0.06mug/ml的菌株中也发现了这种突变。32株菌株只有一种gyrA突变(Ser83-->；Phe；Ser83-->；Tyr；Asp87-->；ASN、Asp87->；Tyr；或Asp87->；Gly)，34株同时存在gyra突变和Parc突变(29株Parc突变为Tyr87-57&Gt；Serr和5株ParC突变为Ser80-->；Arg的菌株)。6株新近分离的菌株(1998年至2001年)对每毫升4杯环丙沙星耐药，其中2株具有双重gyrA突变(Ser83-->；Phe和Asp87-->；asn)和一个parc突变(Ser80-->；Arg)(MIC值为8-32 mug/ml)，其中4株具有双重gyrA突变(Ser83-->；Phe和Asp87->；Gly)，1株parc突变(Ser80-->；Arg)，1株pare突变(Ser458-->；亲)(最低抑菌浓度，16对/毫升)。所有六个分离株和那些Ser80-->；Arg Parc突变的菌株都是肠杆菌血清型鼠伤寒杆菌。一株伤寒沙门氏菌含有单一gyrA突变(Ser83->；Phe)，一株甲型副伤寒沙门氏菌含有gyrA突变(Ser83->；Tyr)和ParC突变(Tyr57->；Ser)；这两株菌株对氟喹诺酮类药物的敏感性均降低。环丙沙星、左氧氟沙星和司帕沙星的MIC总体上是6种氟喹诺酮类药物中最低的。具有单一gyrA突变的菌株对氟喹诺酮类药物的耐药性低于具有附加parc突变(Tyr57-->；Ser或Ser80-->；Arg)的菌株，而具有双gyrA突变的菌株对氟喹诺酮类药物的耐药性更高。
A total of 88 salmonella isolates (72 clinical isolates for which the ciprofloxacin MIC was >0.06 mug/ml, 15 isolates for which the ciprofloxacin MIC was less than or equal to0.06 mug/ml, and Salmonella enterica serotype Typhimurium ATCC 13311) were studied for the presence of genetic alterations in four quinolone resistance genes, gyrA, gyrB, parC, and parE, by multiplex PCR amplimer conformation analysis. The genetic alterations were confirmed by direct nucleotide sequencing. A considerable number of strains had a mutation in parC, the first to be reported in salmonellae. Seven of the isolates sensitive to 0.06 mug of ciprofloxacin per ml had a novel mutation at codon 57 of parC (Tyr57-->Ser) which was also found in 29 isolates for which ciprofloxacin MICs were >0.06 mug/ml. Thirty-two isolates had a single gyrA mutation (Ser83-->Phe, Ser83-->Tyr, Asp87-->Asn, Asp87-->Tyr, or Asp87-->Gly), 34 had both a gyrA mutation and a parC mutation (29 isolates with a parC mutation of Tyr57-->Ser and 5 isolates with a parC mutation of Ser80-->Arg). Six isolates which were isolated recently (from 1998 to 2001) were resistant to 4 mug of ciprofloxacin per ml. Two of these isolates had double gyrA mutations (Ser83-->Phe and Asp87-->Asn) and a parC mutation (Ser80-->Arg) (MICs, 8 to 32 mug/ml), and four of these isolates had double gyrA mutations (Ser83-->Phe and Asp87-->Gly), one parC mutation (Ser80-->Arg), and one parE mutation (Ser458-->Pro) (MICs, 16 to 64 mug/ml). All six of these isolates and those with a Ser80-->Arg parC mutation were S. enterica serotype Typhimurium. One S. enterica serotype Typhi isolate harbored a single gyrA mutation (Ser83-->Phe), and an S. enterica serotype Paratyphi A isolate harbored a gyrA mutation (Ser83-->Tyr) and a parC mutation (Tyr57-->Ser); both of these isolates had decreased susceptibilities to the fluoroquinolones. The MICs of ciprofloxacin, levofloxacin, and sparfloxacin were in general the lowest of those of the six fluoroquinolones tested. Isolates with a single gyrA mutation were less resistant to fluoroquinolones than those with an additional parC mutation (Tyr57-->Ser or Ser80-->Arg), while those with double gyrA mutations were more resistant.