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katG基因第315位氨基酸的突变与对异烟肼的高水平耐药性、其他耐药性以及荷兰结核分枝杆菌的成功传播有关。

Mutations at amino acid position 315 of the katG gene are associated with high-level resistance to isoniazid, other drug resistance, and successful transmission of Mycobacterium tuberculosis in the Netherlands.

作者信息

van Soolingen D, de Haas P E, van Doorn H R, Kuijper E, Rinder H, Borgdorff M W

机构信息

Mycobacteria Reference Laboratory, RIVM (LIS-pb22), 3720 BA Bilthoven, The Netherlands.

出版信息

J Infect Dis. 2000 Dec;182(6):1788-90. doi: 10.1086/317598. Epub 2000 Oct 26.

DOI:10.1086/317598
PMID:11069256
Abstract

The prevalence of mutations at amino acid (aa) position 315 in the katG gene of isoniazid (INH)-resistant Mycobacterium tuberculosis isolates in The Netherlands and the mutation's association with the level of INH resistance, multidrug resistance, and transmission were determined. Of 4288 M. tuberculosis isolates with available laboratory results, 295 (7%) exhibited INH resistance. Of 148 aa 315 mutants, 89% had MICs of 5-10 microg/mL, whereas 75% of the other 130 INH-resistant strains had MICs of 0.5-1 microg/mL. Of the aa 315 mutants, 33% exhibited monodrug resistance, compared with 69% of other INH-resistant strains (P<.0001). Multidrug resistance was found among 14% of the aa 315 mutants and 7% of the other INH-resistant strains (P>.05). The probability of being in an IS6110 DNA restriction fragment length polymorphism cluster was similar for aa 315 mutants and INH-susceptible strains, but the probability was reduced in other INH-resistant strains. Thus, aa 315 mutants lead to secondary cases of tuberculosis as often as INH-susceptible strains do.

摘要

研究了荷兰耐异烟肼(INH)结核分枝杆菌分离株katG基因第315位氨基酸(aa)突变的发生率,以及该突变与INH耐药水平、多药耐药和传播的相关性。在4288株有实验室结果的结核分枝杆菌分离株中,295株(7%)表现出INH耐药。在148株第315位氨基酸突变株中,89%的最低抑菌浓度(MIC)为5 - 10μg/mL,而其他130株耐INH菌株中75%的MIC为0.5 - 1μg/mL。在第315位氨基酸突变株中,33%表现出单药耐药,而其他耐INH菌株中这一比例为69%(P<0.0001)。14%的第315位氨基酸突变株和7%的其他耐INH菌株存在多药耐药(P>0.05)。第315位氨基酸突变株和INH敏感菌株在IS6110 DNA限制性片段长度多态性簇中的概率相似,但其他耐INH菌株的概率降低。因此,第315位氨基酸突变株导致结核病二代病例的情况与INH敏感菌株一样常见。

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