Association of specific mutations in katG, rpoB, rpsL and rrs genes with spoligotypes of multidrug-resistant Mycobacterium tuberculosis isolates in Russia
Association of specific mutations in katG, rpoB, rpsL and rrs genes with spoligotypes of multidrug-resistant Mycobacterium tuberculosis isolates in Russia
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DOI：
10.1111/j.1469-0691.2007.01711.x
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发表时间：
2007-06-01
影响因子：
14.2
通讯作者：
Shinnick, T. M.
中科院分区：
文献类型：
--
作者：
Lipin, M. Y.;Stepanshina, V. N.;Shinnick, T. M.
俄罗斯的大多数多药耐药（MDR）结核分枝杆菌分离株属于北京或拉丁美洲和地中海（LAM）spoligotype家族。本研究的目的是调查基因型和突变频率之间的可能关联，赋予耐药性的人群中有两个大家族的循环菌株。对217例MDR M进行Spoligotyping、IS 6110限制性片段长度多态性分型和katG和rpoB基因测序。结核病从病人身上分离出来。rpsL和rrs基因也被测序选定的链霉素耐药菌株。在217株MDR菌株中，LAM家族99株（46%），北京家族92株（42%），哈勒姆家族21株（10%），T家族4株（2%）。有一个独特的spoligotype。在207（95%）分离株中鉴定了katG基因突变，所有这些分离株均在密码子315处发生突变。在200株（92%）分离株中鉴定出rpoB基因突变; 75%的LAM分离株在密码子516处携带突变，而71%的北京分离株在密码子531处携带突变。对链霉素50 mg/L耐药的33株分离株中，27%的哈勒姆、75%的北京和0%的LAM分离株存在43 AGG rpsL突变，17%的北京和100%的LAM分离株存在rrs突变（516 C-> T）。总的来说，在北京和LAM家族中，基因型和特定突变之间似乎存在相关性，这些突变赋予了对利福平或链霉素的抗性。这种相关性的生物学意义仍有待探索。
Most multidrug-resistant (MDR) Mycobacterium tuberculosis isolates in Russia belong to the Beijing or Latino-American and Mediterranean (LAM) spoligotype families. The objective of this study was to investigate possible associations between genotype and the frequencies of mutations that confer drug resistance in a population that has two large families of circulating strains. Spoligotyping, IS6110 restriction fragment length polymorphism typing, and sequencing of the katG and rpoB genes, were performed for 217 consecutive MDR M. tuberculosis isolates from patients. The rpsL and rrs genes were also sequenced for selected streptomycin-resistant isolates. Of the 217 MDR isolates, 99 (46%) belonged to the LAM family, 92 (42%) to the Beijing family, 21 (10%) to the Haarlem family and four (2%) to the T family. There was one unique spoligotype. Mutations in the katG gene were identified in 207 (95%) isolates, all of which had mutations in codon 315. Mutations in the rpoB gene were identified in 200 (92%) isolates; 75% of LAM isolates carried a mutation in codon 516, whereas 71% of Beijing isolates carried a mutation in codon 531. In the 33 isolates resistant to streptomycin 50 mg/L, the 43AGG rpsL mutation was found in 27% of Haarlem, 75% of Beijing and 0% of LAM isolates, and rrs mutations were found in 17% (516C -> T) of Beijing and 100% (513A -> C) of LAM isolates. Overall, there appeared to be a correlation between the genotype and specific mutations conferring resistance to rifampicin or streptomycin in the Beijing and LAM families. The biological implications of this correlation remain to be explored.