热带病与寄生虫学 ›› 2023, Vol. 21 ›› Issue (2): 82-87.doi: 10.3969/j.issn.1672-2302.2023.02.005
叶婧1(), 周崇兴1, 林玫1, 先晓敏2, 梁小烟1, 张影坤1, 蓝如束3, 崔哲哲1(
)
收稿日期:
2023-03-17
出版日期:
2023-04-20
发布日期:
2023-05-03
通信作者:
崔哲哲,E-mail: 作者简介:
叶婧,女,硕士,主管技师,研究方向:传染病流行病学。E-mail: 基金资助:
YE Jing1(), ZHOU Chong-xing1, LIN Mei1, XIAN Xiao-min2, LIANG Xiao-yan1, ZHANG Ying-kun1, LAN Ru-shu3, CUI Zhe-zhe1(
)
Received:
2023-03-17
Online:
2023-04-20
Published:
2023-05-03
Contact:
CUI Zhe-zhe, E-mail: 摘要:
目的 分析广西边境地区和非边境地区结核分枝杆菌(Mycobacterium tuberculosis,MTB)基因型和耐药相关基因的分布特征。方法 收集2015—2017年广西五个地区的结核病定点医疗机构的患者痰液标本,对边境地区(边境组)和非边境地区(非边境组)的MTB分离培养株进行对比研究。采用二代全基因组高通量测序技术对菌株进行基因分型,鉴定MTB菌株谱系,收集MTB耐药基因的变化信息。结果 研究共纳入646株菌株。边境组199株,其中Lineage 1有8株(占4.02%),Lineage 2有126株(占63.32%),Lineage 3有1株(占0.01%),Lineage 4有64株(占32.16%);非边境组447株,其中Lineage 1有4株(占0.89%),Lineage 2有299株(占66.89%),Lineage 4有144株(占32.21%),Lineage 3未见。边境组与非边境组基因型构成差异有统计学意义(χ2=9.754,P<0.05)。其中Lineage 1和Lineage 4.2基因型在边境组和非边境组的分布差异有统计学意义(χ2=5.763、4.833,P均<0.05)。有196株MTB分离株发生了耐药相关基因突变,其中边境组突变率(40.70%,81/199)高于非边境组(25.73%,115/447)(χ2=14.613,P<0.05)。突变率前5的耐药基因依次是katG(15.94%,103/646)、ropB(11.30%,73/646)、embB(6.04%,39/646)、rpsL(5.88%,38/646)和 rrsL(3.72%,24/646)。其中katG、ropB、rpsL基因在边境组的突变率均高于非边境组(χ2=5.716、9.603、6.979,P均<0.05),对应的katG315、rpoB450、rpsL43基因位点在边境组与非边境组的分布差异也均具有统计学意义(χ2=5.153、12.893、11.693,P均<0.05)。结论 广西MTB菌株出现 Lineage 1和Lineage 3谱系,可能从邻国传入,需要进一步研究。广西耐药相关基因位点突变的分布与MTB基因型构成有一定的相关性。
中图分类号:
叶婧, 周崇兴, 林玫, 先晓敏, 梁小烟, 张影坤, 蓝如束, 崔哲哲. 广西边境地区与非边境地区结核分枝杆菌基因组学分析[J]. 热带病与寄生虫学, 2023, 21(2): 82-87.
YE Jing, ZHOU Chong-xing, LIN Mei, XIAN Xiao-min, LIANG Xiao-yan, ZHANG Ying-kun, LAN Ru-shu, CUI Zhe-zhe. Genomic analysis of Mycobacterium tuberculosis in border and non-border areas of Guangxi Zhuang Autonomous Region[J]. Journal of Tropical Diseases and Parasitology, 2023, 21(2): 82-87.
表3
广西边境组和非边境组MTB菌株基因型分布[n(%)]
谱系 | 边境组 | 非边境组 | χ2值 | P值 |
---|---|---|---|---|
L1 | 8(4.02) | 4(0.89) | 5.763 | <0.05 |
L2 | 126(63.32) | 299(66.59) | 0.781 | >0.05 |
L2.1 | 11(5.53) | 29(6.49) | 0.219 | >0.05 |
L2.2 | 43(21.61) | 107(23.94) | 0.419 | >0.05 |
L2.3 | 72(36.18) | 163(36.47) | 0.005 | >0.05 |
L3 | 1(0.50) | 0(0) | >0.05* | |
L4 | 64(32.16) | 144(32.21) | 0.000 | >0.05 |
L4.1.2 | 0(0) | 1(0.22) | >0.05* | |
L4.2 | 9(4.52) | 43(9.62) | 4.833 | <0.05 |
L4.3 | 0(0) | 1(0.22) | >0.05* | |
L4.4 | 37(18.59) | 57(12.75) | 3.779 | >0.05 |
L4.5 | 15(7.54) | 32(7.16) | 0.029 | >0.05 |
L4.7 | 1(0.50) | 2(0.45) | >0.05* | |
L4.9 | 2(1.00) | 8(1.79) | 0.161 | >0.05 |
表4
MTB分离株耐药基因突变在广西边境与非边境地区的分布[n(%)]
药物 | 耐药基因 | 总菌株数 | 组别 | χ2值 | P值 | |
---|---|---|---|---|---|---|
边境组 | 非边境组 | |||||
异烟肼 | katG | 103(15.94) | 42(21.11) | 61(13.65) | 5.716 | <0.05 |
fabG1 | 11(1.70) | 5(2.51) | 6(1.34) | 0.536 | >0.05 | |
ahpC | 7(1.08) | 2(1.01) | 5(1.12) | <0.001 | >0.05 | |
inhA | 3(0.46) | 1(0.50) | 2(0.45) | >0.05* | ||
利福平 | rpoB | 73(11.30) | 34(17.09) | 39(8.72) | 9.603 | <0.01 |
乙胺丁醇 | embB | 39(6.04) | 15(7.54) | 24(5.37) | 1.142 | >0.05 |
embC | 14(2.17) | 8(4.02) | 6(1.34) | 3.480 | >0.05 | |
链霉素 | rpsL | 38(5.88) | 19(9.55) | 19(4.25) | 6.979 | <0.01 |
rrsL | 24(3.72) | 4(2.01) | 20(4.47) | 2.337 | >0.05 | |
吡嗪酰胺 | pncA | 20(3.10) | 9(4.52) | 11(2.46) | 1.951 | >0.05 |
表5
MTB分离株耐药基因突变位点在广西边境与非边境地区的分布
基因 | 位点 | 碱基的改变 | 氨基酸的改变 | 组别 | χ2值 | P值 | |
---|---|---|---|---|---|---|---|
边境组[n(%)] | 非边境组[n(%)] | ||||||
katG | 315 | AGC→ACC | 丝氨酸→苏氨酸 | 38(19.10) | 55(12.30) | 5.153 | <0.05 |
rpoB | 450 | TCG→TTG | 丝氨酸→亮氨酸 | 19(9.55) | 13(2.91) | 12.893 | <0.01 |
rpoB | 445 | CAC→CCC | 组氨酸→脯氨酸 | 7(3.52) | 12(2.68) | 0.335 | >0.05 |
CAC→TAC | 组氨酸→酪氨酸 | ||||||
CAC→GAC | 组氨酸→天门冬氨酸 | ||||||
CAC→AAC | 组氨酸→天门冬氨酸 | ||||||
CAC→CGC | 组氨酸→精氨酸 | ||||||
embB | 306 | ATG→GTG | 甲硫氨酸→缬氨酸 | 10(5.03) | 15(3.36) | 1.032 | >0.05 |
ATG→ATT | 甲硫氨酸→异亮氨酸 | ||||||
ATG→ATC | 甲硫氨酸→异亮氨酸 | ||||||
ATG→ATA | 甲硫氨酸→异亮氨酸 | ||||||
rpsL | 43 | AAG→AGG | 赖氨酸→精氨酸 | 19(9.55) | 14(3.13) | 11.693 | <0.01 |
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