结核分枝杆菌北京基因型亚型的流行及与耐药性的关系研究

Ancient Mycobacterium tuberculosis Beijing genotype clinical isolates are associated with drug resistance in Tianjin, China

目的通过分析Mtb北京基因型基因组NTF（noisetransferfunction）区插入序列IS6110，揭示北京基因型在进化过程中所形成的古代株和现代株2个亚型在天津市的流行情况及其与耐药表型的关系。方法收集20122014年天津市临床分离的816株Mtb菌株。采用PCR试验分析菌株基因组中差异区域（Regionofdifference，RD）RD207和RD105片段是否有缺失，以鉴定是否为北京基因型。通过检测北京基因型菌株基因组NTF区中IS6110插入序列的数目，了解北京基因型菌株中古代株和现代株所占的比例，并进一步分析这两种亚型与菌株耐药表型间的关系。计数资料采用卡方检验进行分析，以P〈0．05为差异有统计学意义。结果在所分析的816株临床分离的Mtb菌株中，764（93．63％）株为北京基因型菌株。764株北京基因型菌株中，110株（14．40％）为古代株，654株（85．60％）为现代株。现代株中仅有1株为北京基因型w株。在古代株和现代株中，耐异烟肼菌株分别占26．36％（29／110）和10．70％（70／654）（X2=20．47，P〈0．01）；耐利福平菌株分别占14．55％（16／110）和6．57％（43／654）（X2=8．40，P〈0．01）；耐乙胺丁醇菌株分别占8．18％（9／110）和3．21％（21／654），（X2=6．17，P〈0．05）。此外，MDR-TB患者中古代株和现代株分别占13．64％（15／110）和4．74％（31／654）（X2=13．17，P〈0．01）。结论Mtb北京基因型中的现代株是天津市的主要流行株，但古代株与耐药结核病的关系更为密切，提示在天津市，对抗结核药物产生耐药并不是导致北京基因型广泛流行的主要因素。

Objective Mycobacterium tuberculosis （Mtb） Beijing genotype strains are globally distributed and have evolved a variety of sublineages. Based on the absence or presence of IS6110 insertions in the noise transfer function （NTF） chromosomal region, Beijing genotype strains can be divided into two sublineages, known as ancient （atypical） and modern （typical） strains. This study aimed to investigate the prevalence of Beijing sublineages and the relationship between these sublineages and drug-resistance. Methods A total of 816 clinical isolates of Mtb from 2012 to 2014 were used. Deletion of Region of difference （RD） 207 and RD105 was detected using PCR to identify Bei）ing genotype isolates. Numbers of IS6110 insertions in the NTF region in the Beijing strains were deter- mined and the association between Beijing genotype sublineage and drug-resistance was analyzed. Results Of the 816 isolates examined, 764 （93.63%） strains belonged to the Beijing genotype. Of these, 110 （14.40%） were ancient strains, and 654 （85.60%） strains were modern strains. One modern strain belonged to W strain, which had two IS6110 insertions in the NTF region. Ancient Beijing strains were more highly represented than modern Beijing stains among isoniazide-resistant （26.36% vs 10.70% ）（.z =20.47, P〈0.01）, rifampin-resistant （14.55% vs 6.57%, X2=8. 40, P〈0.01） and ethambutol-resistant （8.18% vs 3.21%, X2 =6.17, P〈0.05） strains. Pro- portions of ancient Beijing strains were significantly higher than those of modern Beijing stains among MDR-TB strains （13.64% vs 4. 74%, Z2 =13. 17, P〈0.01）. Conclusion Modern Beijing strains are predominant in China, and ancient Beijing strains exhibit a greater association with drug resistance. Our findings imply that drug resistance may not be the major factor driving Beijing genotype transmission in Tianjin, China.