蛔虫β-管蛋白基因家族中的单核苷酸多态性及其在苯并咪唑抗药性中的潜在作用:系统综述

Teniel Ramkhelawan, Pragalathan Naidoo, Z. Mkhize-Kwitshana
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引用次数: 0

摘要

最常见的土壤传播蠕虫感染是由蛔虫(A. lumbricoides)引起的。全球约有 40 亿人面临感染风险。世界卫生组织建议对所有易感人群使用含苯并咪唑的驱虫药(阿苯达唑和甲苯达唑)。由于药物压力大,这些寄生虫可能会对目前的苯并咪唑类药物产生抗药性。β-管蛋白基因家族是苯并咪唑类驱虫药的靶基因。本系统综述旨在突出探讨与潜在苯并咪唑抗药性相关的蓝线蛔虫β-管蛋白基因家族基因突变的研究工作。腰缠蛔虫的 β-管蛋白基因家族中,密码子 F200Y(TTC/苯丙氨酸变为 TAC/酪氨酸)、E198A(GAG、GAA/谷氨酸变为 GCG、GCA/丙氨酸)和 F167Y(TTC、TTT/苯丙氨酸变为 TAC、TAT/酪氨酸)突变与潜在的苯并咪唑抗药性有关。在海地、肯尼亚和巴拿马的腰蛔虫样本中发现了密码子 F167Y 的抗性突变。在巴西首次发现了密码子 F200Y 突变的证据。对流行地区腰缠蛔虫种群中β-微管蛋白基因家族突变发生率的调查研究严重不足;这是一个令人严重关切的问题,因为抗药性将对目前的大规模用药计划产生负面影响。
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Single nucleotide polymorphisms in the β-tubulin gene family of Ascaris lumbricoides and their potential role in benzimidazole resistance: a systematic review
The most common soil-transmitted helminthic infection is caused by Ascaris lumbricoides (A. lumbricoides). Approximately 4 billion people are at risk of infection globally. The World Health Organisation recommends the administration of benzimidazole- containing deworming drugs (Albendazole and Mebendazole) to all susceptible populations. Due to this high drug pressure, these parasites may develop resistance to current benzimidazole drugs. The β-tubulin gene family is the target gene for benzimidazole deworming drugs. This systematic review aimed to highlight work that explored the genetic mutations in the β-tubulin gene family of A. lumbricoides that are associated with potential benzimidazole resistance.An electronic search of several online databases was used to extract eligible articles using specific keywords related to the topic of interest.The majority of ascariasis infections occur in the subtropical and tropical regions of sub-Saharan Africa, the Americas and East Asia, although not enough studies were done to extensively cover this geographical range. In the β-tubulin gene family of A. lumbricoides the mutations at codons F200Y (TTC/Phenylalanine to TAC/Tyrosine), E198A (GAG, GAA/Glutamic acid to GCG, GCA/Alanine) and F167Y (TTC, TTT/Phenylalanine to TAC, TAT/Tyrosine) were associated with potential benzimidazole resistance.Resistant mutations were found in A. lumbricoides samples at codon F167Y from Haiti, Kenya and Panama. The first evidence of the mutation at codon F200Y was observed in Brazil. The codon E198A mutation was the least prevalent and most undetected.There is a serious shortage of studies investigating the prevalence of β-tubulin gene family mutations in A. lumbricoides populations from endemic areas; this is a serious concern as resistance will negatively impact current mass drug administration programmes.
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