【摘要】 本文利用伤寒沙门菌２７５（临床敏感菌株）及其耐喹诺酮类自发变异株ＲＧ１，测定其ＤＮＡ旋转酶Ａ业单位基因（ｇｙｒＡ）喹诺酮类耐药决定区（ＱＲＤＲ）碱基序列，分析药物与细菌相互作用关系。结果发现伤寒沙门菌２７５ ｇｙｒＡ第１２８－４３４位碱基与大肠埃希菌ＫＬ－１６、鼠伤寒沙门菌ＮＣＴＣ ７４及铜绿假单胞菌ＰＡＯＩ相应碱基有９２．５１％、９７．２２％及７７．３５％同源性，推定氨基酸仅有３、 ２及１３处变异；伤寒沙菌ＲＧＩ ｇｙｒＡ仅于第２４７位碱基由Ｔ→ Ｇ％异，相应第８３位氨基酸由Ｓｅｒ→Ａｌａ改变，使药物与ＤＮＡ旋转酶亲合力降低，萘啶酸、氧氟沙星、环丙沙星对伤寒沙门菌ＲＧＩ的ＭＩＣ值较对伤寒沙门菌２７５增加３２倍以上。上述结果提示喹诺酮类抗伤寒沙门菌机制与其它细菌相同，ｇｙｒＡ ＱＲＤＲ变异是伤寒沙门菌耐药的主要原因。更多还原

【Abstract】 Quinolone-resistant determining region (QRDR) of DNA phrase gyrA genes from Salmonella typhi 275 (a clinically isolated quinolone susceptible strain) and its spontaneous quinolone resistant mutant S.typhi RG1 were sequenced and the interaction between quinolones and DNA gyrase was analyzed. The results revealed that the 128-434 nucleotide sequence of S. typhi 275 gyrA were 92.51%, 97.72% and 77.35% identical with those of Escherichia colt KL-16,S. typhimirum NCTC 74 and Pseudomonas aeruginosa PAO1, which contributed to 3、2 and 13 differences, respectively, in the deduced amino acids in each bacteria. In comparision with S. typhi 275, a single mutation was found at base 247 in gyrA of S. typhi RGI, which changed from T to G and led to an amino acid substitution of Ser83Ala. The mutation might be resposible for the increase of MICs of nalidixic acid, ofloxacin and ciprofloxacin on S.typhi from 2, 0.06, <0.03 to 512, 2, 1mg/L, respectively. These results indicated that the antibacterial mechanism of quinolone on S. typhi was the same as those on the other bacteria and that the mutation in QRDR of gyrA was also the major reason for quinolone resistance in S. typhi.更多还原