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埃塞俄比亚流行谱系的比较生长动力学和药物敏感性:对结核病治疗与管理的影响

Comparative growth kinetics and drug susceptibility of lineages prevalent in Ethiopia: implications for tuberculosis treatment and management.

作者信息

Hailemariam Tesfaye Gebreyohannis, Tilahun Melaku, Atnafu Abay, Gelanew Tesfaye, Gebresilase Tewodros Tariku, Tola Mekdes Alemu, Ayele Abaysew, Siraj Shewki Moga, Shibeshi Workineh, Bobosha Kidist, Wassie Liya, Hirutu Yonas, Engidawork Ephrem

机构信息

Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Armauer Hansen Research Institute (AHRI), Addis Ababa, Ethiopia.

出版信息

Front Microbiol. 2025 Feb 4;15:1512580. doi: 10.3389/fmicb.2024.1512580. eCollection 2024.

DOI:10.3389/fmicb.2024.1512580
PMID:39968044
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11832462/
Abstract

Tuberculosis (TB) remains a global health challenge, with treatment outcomes influenced by the genetic diversity of () strains. This study examines the growth kinetics and drug susceptibility of strains from different lineages in Ethiopia to understand their impact on disease management. strains, including sub-lineages 4.1.2.1, 4.2.2.2, 4.6.3, lineages 3 and 7, and the reference strain H37Rv (ATCC 27294), were cultured in liquid 7H9 Middlebrook broth. Growth began on day 6 post-inoculation. Sub-lineage 4.1.2.1 showed rapid exponential growth by day 9, reaching the stationary phase by day 15. Sub-lineage 4.1.2.1 followed by sub-lineage 4.2.2.2 had the highest maximum growth concentration ( ), indicating enhanced growth efficiency and adaptive traits that may increase their pathogenicity or resistance to host defenses or anti-TB drugs. To support this observation, the minimum inhibitory concentrations (MIC) for first-line anti-TB drugs were assessed for all the studied strains using the microdilution broth method. While all strains were susceptible, MIC values varied. Sub-lineages 4.1.2.1 and 4.2.2.2 had MIC values matching WHO's critical concentrations (except for rifampicin). Lineage 3 showed increased sensitivity to rifampicin, isoniazid, and streptomycin, requiring only half the standard concentration. Lineage 7 also exhibited higher sensitivity to rifampicin and streptomycin. These findings highlight the importance of considering lineage-specific differences in strains for optimizing treatment regimens and improving TB control strategies, particularly in regions with diverse populations like Ethiopia.

摘要

结核病(TB)仍然是一项全球性的健康挑战,其治疗结果受到结核分枝杆菌菌株遗传多样性的影响。本研究考察了埃塞俄比亚不同谱系的结核分枝杆菌菌株的生长动力学和药物敏感性,以了解它们对疾病管理的影响。将包括亚谱系4.1.2.1、4.2.2.2、4.6.3、谱系3和7以及参考菌株H37Rv(ATCC 27294)在内的结核分枝杆菌菌株在液体7H9 Middlebrook肉汤中培养。接种后第6天开始生长。亚谱系4.1.2.1在第9天显示出快速指数生长,到第15天达到稳定期。亚谱系4.1.2.1随后是亚谱系4.2.2.2具有最高的最大生长浓度,表明生长效率提高以及可能增加其致病性或对宿主防御或抗结核药物抗性的适应性特征。为支持这一观察结果,使用微量稀释肉汤法评估了所有研究的结核分枝杆菌菌株对一线抗结核药物的最低抑菌浓度(MIC)。虽然所有菌株均敏感,但MIC值有所不同。亚谱系4.1.2.1和4.2.2.2的MIC值与世界卫生组织的临界浓度相符(利福平除外)。谱系3对利福平、异烟肼和链霉素表现出更高的敏感性,仅需要标准浓度的一半。谱系7对利福平和平链霉素也表现出更高的敏感性。这些发现凸显了在优化治疗方案和改进结核病控制策略时考虑结核分枝杆菌菌株谱系特异性差异的重要性,特别是在像埃塞俄比亚这样具有多样化结核分枝杆菌种群的地区。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5896/11832462/8fcaf398b650/fmicb-15-1512580-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5896/11832462/143e85e01062/fmicb-15-1512580-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5896/11832462/e93464a5279b/fmicb-15-1512580-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5896/11832462/8fcaf398b650/fmicb-15-1512580-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5896/11832462/143e85e01062/fmicb-15-1512580-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5896/11832462/e93464a5279b/fmicb-15-1512580-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5896/11832462/8fcaf398b650/fmicb-15-1512580-g003.jpg

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本文引用的文献

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Sci Rep. 2024 May 7;14(1):10455. doi: 10.1038/s41598-024-59435-3.
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Global, regional and national trends in tuberculosis incidence and main risk factors: a study using data from 2000 to 2021.全球、区域和国家结核病发病率及主要危险因素趋势:基于 2000 至 2021 年数据的研究。
BMC Public Health. 2024 Jan 2;24(1):12. doi: 10.1186/s12889-023-17495-6.
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Sub-Lineage 4.2.2/SIT149 as Dominant Drug-Resistant Clade in Northwest Ethiopia 2020-2022: In-silico Whole-Genome Sequence Analysis.
2020 - 2022年埃塞俄比亚西北部以亚分支4.2.2/SIT149作为主要耐药分支:全基因组序列的电子分析
Infect Drug Resist. 2023 Oct 26;16:6859-6870. doi: 10.2147/IDR.S429001. eCollection 2023.
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Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of complex.缺乏甲氧基-mycolates 是复杂的地理上受限谱系 7 的特征。
Microb Genom. 2023 May;9(5). doi: 10.1099/mgen.0.001011.
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TBProfiler for automated calling of the association with drug resistance of variants in Mycobacterium tuberculosis.TBProfiler 用于自动检测结核分枝杆菌变异与耐药性的关联。
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