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本文引用的文献

1
Genotypic profile of benzimidazole resistance associated with SNP F167Y in the beta-tubulin gene of Necator americanus helminths obtained from Brazilian populations.从巴西人群中获得的美洲钩虫β-微管蛋白基因 SNP F167Y 相关的苯并咪唑耐药的基因型特征。
Infect Genet Evol. 2020 Dec;86:104594. doi: 10.1016/j.meegid.2020.104594. Epub 2020 Oct 17.
2
Teladorsagia circumcincta beta tubulin: the presence of the E198L polymorphism on its own is associated with benzimidazole resistance.细颈线虫β微管蛋白:其 E198L 多态性的存在本身与苯并咪唑类药物抗性相关。
Parasit Vectors. 2020 Sep 7;13(1):453. doi: 10.1186/s13071-020-04320-x.
3
First identification of the benzimidazole resistance-associated F200Y SNP in the beta-tubulin gene in Ascaris lumbricoides.首次在猪蛔虫β-微管蛋白基因中发现与苯并咪唑类药物耐药相关的 F200Y SNP。
PLoS One. 2019 Oct 17;14(10):e0224108. doi: 10.1371/journal.pone.0224108. eCollection 2019.
4
High Endemicity of Soil-Transmitted Helminths in a Population Frequently Exposed to Albendazole but No Evidence of Antiparasitic Resistance.在经常接触阿苯达唑的人群中土壤传播蠕虫的高流行率,但无抗寄生虫耐药性证据。
Trop Med Infect Dis. 2019 Apr 27;4(2):73. doi: 10.3390/tropicalmed4020073.
5
Albendazole resistance induced in Ancylostoma ceylanicum is not due to single-nucleotide polymorphisms (SNPs) at codons 167, 198, or 200 of the beta-tubulin gene, indicating another resistance mechanism.在锡兰钩虫中诱导产生的阿苯达唑抗性并非由于β-微管蛋白基因第167、198或200位密码子的单核苷酸多态性(SNP),这表明存在另一种抗性机制。
Parasitol Res. 2019 Mar;118(3):837-849. doi: 10.1007/s00436-019-06218-9. Epub 2019 Jan 29.
6
Molecular detection of benzimidazole resistance levels associated with F167Y and F200Y polymorphisms in Haemonchus contortus of goats from Mozambique.莫桑比克山羊捻转血矛线虫中与F167Y和F200Y多态性相关的苯并咪唑抗性水平的分子检测
Parasitol Res. 2019 Jan;118(1):245-253. doi: 10.1007/s00436-018-6162-6. Epub 2018 Dec 13.
7
Deep amplicon sequencing as a powerful new tool to screen for sequence polymorphisms associated with anthelmintic resistance in parasitic nematode populations.深度扩增子测序作为一种强大的新工具,用于筛选与寄生虫线虫种群中抗寄生虫药物耐药性相关的序列多态性。
Int J Parasitol. 2019 Jan;49(1):13-26. doi: 10.1016/j.ijpara.2018.10.005. Epub 2018 Nov 22.
8
Standardization and application of a modified RFLP-PCR methodology for analysis of polymorphisms linked to treatment resistance in Ancylostoma braziliense.改良 RFLP-PCR 方法分析与巴西钩虫治疗耐药性相关多态性的标准化及应用。
Parasit Vectors. 2018 Oct 9;11(1):540. doi: 10.1186/s13071-018-3125-9.
9
PCR-RFLP screening of polymorphisms associated with benzimidazole resistance in Necator americanus and Ascaris lumbricoides from different geographical regions in Brazil.巴西不同地区的美洲板口线虫和蛔虫中与苯并咪唑类药物耐药性相关的多态性的 PCR-RFLP 筛选。
PLoS Negl Trop Dis. 2018 Sep 17;12(9):e0006766. doi: 10.1371/journal.pntd.0006766. eCollection 2018 Sep.
10
Soil-transmitted helminth infections.土壤传播的蠕虫感染。
Lancet. 2018 Jan 20;391(10117):252-265. doi: 10.1016/S0140-6736(17)31930-X. Epub 2017 Sep 4.

巴西人群中毛首鞭形线虫β-微管蛋白基因中苯并咪唑抗性相关单核苷酸多态性的检测

Detection of Benzimidazole Resistance-Associated Single-Nucleotide Polymorphisms in the Beta-Tubulin Gene in Trichuris trichiura from Brazilian Populations.

作者信息

Mendes de Oliveira Valéria Nayara Gomes, Zuccherato Luciana Werneck, Dos Santos Talita Rodrigues, Rabelo Élida Mara Leite, Furtado Luis Fernando Viana

机构信息

Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Belo Horizonte, Minas Gerais, Brazil.

Universidade do Estado de Minas Gerais, Unidade Passos, Minas Gerais, Brazil.

出版信息

Am J Trop Med Hyg. 2022 Jul 25;107(3):640-8. doi: 10.4269/ajtmh.22-0157.

DOI:10.4269/ajtmh.22-0157
PMID:35895340
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9490667/
Abstract

Preventive chemotherapy is recommended by the WHO as the main strategy for controlling infections caused by nematodes in humans, aiming to eliminate the morbidity associated with these infections. This strategy consists of routine periodic administration of benzimidazoles, among other drugs. Although these drugs decrease the intensity of infections, they have the potential to exert selection pressure for genotypes bearing mutations associated with drug resistance, which may result in the establishment of resistant worm populations. There is evidence in the literature of resistance to these drugs in nematodes that infect humans, including in the species Trichuris trichiura. Single-nucleotide polymorphisms (SNPs) in the beta-tubulin gene located at codons 167, 198, and 200 are associated with the mechanism of resistance to benzimidazoles in nematodes. Here, we standardized a molecular technique based on an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) to analyze codons 167, 198, and 200 of T. trichiura. The ARMS-PCR methodology was successfully established to evaluate the codons of interest. A total of 420 samples of individual eggs were analyzed from populations obtained from five Brazilian states. A mutation in codon 198 was observed at a frequency of 4.8% (20/420), while for the other two codons, no polymorphism was observed. This is the first report of the presence of this mutation in populations of T. trichiura in Brazil. This fact and the emergence of the problem already observed in other species reinforces the need for regular monitoring of SNPs related to benzimidazole resistance using techniques that are highly sensitive and specific.

摘要

世界卫生组织推荐预防性化疗作为控制人类线虫感染的主要策略,旨在消除与这些感染相关的发病率。该策略包括定期常规施用苯并咪唑等药物。尽管这些药物可降低感染强度,但它们有可能对携带与耐药性相关突变的基因型施加选择压力,这可能导致耐药虫种群的形成。文献中有证据表明,包括毛首鞭形线虫在内的感染人类的线虫对这些药物存在耐药性。位于密码子167、198和200处的β-微管蛋白基因中的单核苷酸多态性(SNP)与线虫对苯并咪唑的耐药机制有关。在此,我们基于扩增阻滞突变系统-聚合酶链反应(ARMS-PCR)标准化了一种分子技术,以分析毛首鞭形线虫的密码子167、198和200。成功建立了ARMS-PCR方法来评估感兴趣的密码子。对来自巴西五个州的种群的420个单个虫卵样本进行了分析。观察到密码子198处的突变频率为4.8%(20/420),而对于其他两个密码子,未观察到多态性。这是巴西毛首鞭形线虫种群中存在这种突变的首次报告。这一事实以及在其他物种中已经观察到的问题的出现,强化了使用高度敏感和特异的技术定期监测与苯并咪唑耐药性相关的SNP的必要性。