Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones.
Clonal amplification of Fasciola hepatica in Galba truncatula: within and between isolate variation of triclabendazole-susceptible and -resistant clones.
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DOI：
10.1186/s13071-018-2952-z
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发表时间：
2018-06-26
影响因子：
3.2
通讯作者：
Williams DJL
中科院分区：
文献类型：
--
作者：
Hodgkinson JE;Cwiklinski K;Beesley N;Hartley C;Allen K;Williams DJL
肝片吸虫具有世界性意义，对家畜的健康、福利和生产力产生影响，被世卫组织视为一种重新出现的人畜共患病。三氯苯达唑(TCBZ)是控制牲畜急性肝片吸虫病的首选药物，也是用于治疗人类感染的药物。然而，TCBZ耐药性现在被认为是有效控制肝片吸虫的主要威胁。目前尚不清楚肝片吸虫是否在钉螺中间宿主Galba truncatula中经历了基因克隆扩张，以及钉螺内基因的扩增在多大程度上促进了耐药寄生虫的积累。关于肝片吸虫分离株内部和之间的基因型别和表型变异知之甚少。共获得6株肝片吸虫克隆株(3×三氯苯达唑耐药株TCBZ-R和3×三氯苯达唑敏感株TCBZ-S)。感染一条毛滴虫的钉螺在感染后42-56天开始排出尾蚴，最多重复排出11次。一只克隆感染的钉螺(FhLivS1)在一个时间点上最多排出884个尾蚴，一生中有3000个克隆尾蚴排出。在实验感染后，12只绵羊在接受TCBZ治疗时全部呈FEC阳性。感染三个TCBZ-S克隆中的一个并经TCBZ处理的绵羊在死后肝脏中没有寄生虫，而每一只感染TCBZ-R的绵羊在死后有35-165个成虫，尽管使用了TCBZ处理。所有六只未经处理的对照动物都有15-127种寄生虫。从6个克隆分离株中的每一个吸虫中都报告了一个单一的多位点基因型。肝片吸虫成虫的体重有相当大的差异，从20-280毫克不等，克隆株内和克隆株之间的重量差异明显。在元胞原虫中发生了基因克隆扩增，突出了扩增肝片吸虫耐药基因的潜力。在克隆分离株内和克隆分离株之间以及在比较对TCBZ敏感或抗药性的分离株时，寄生虫重量的变化代表肝吸虫的固有差异，不能归因于它们的抗性或敏感性特征。
Fasciola hepatica is of worldwide significance, impacting on the health, welfare and productivity of livestock and regarded by WHO as a re-emerging zoonosis. Triclabendazole (TCBZ), the drug of choice for controlling acute fasciolosis in livestock, is also the drug used to treat human infections. However TCBZ-resistance is now considered a major threat to the effective control of F. hepatica. It has yet to be demonstrated whether F. hepatica undergoes a genetic clonal expansion in the snail intermediate host, Galba truncatula, and to what extent amplification of genotypes within the snail facilitates accumulation of drug resistant parasites. Little is known about genotypic and phenotypic variation within and between F. hepatica isolates. Six clonal isolates of F. hepatica (3× triclabendazole-resistant, TCBZ-R and 3× triclabendazole-susceptible, TCBZ-S) were generated. Snails infected with one miracidium started to shed cercariae 42–56 days post-infection and shed repeatedly up to a maximum of 11 times. A maximum of 884 cercariae were shed by one clonally-infected snail (FhLivS1) at a single time point, with > 3000 clonal metacercariae shed over its lifetime. Following experimental infection all 12 sheep were FEC positive at the time of TCBZ treatment. Sheep infected with one of three putative TCBZ-S clones and treated with TCBZ had no parasites in the liver at post-mortem, whilst sheep each infected with putative TCBZ-R isolates had 35–165 adult fluke at post-mortem, despite TCBZ treatment. All six untreated control animals had between 15–127 parasites. A single multi-locus genotype was reported for every fluke from each of the six clonal isolates. Adult F. hepatica showed considerable variation in weight, ranging from 20–280 mg, with variation in weight evident within and amongst clonal isolates. A genetic clonal expansion occurs within G. truncatula, highlighting the potential for amplification of drug resistant genotypes of F. hepatica. Variation in the weight of parasites within and between clonal isolates and when comparing isolates that are either susceptible or resistant to TCBZ represent inherent variation in liver fluke and cannot be attributed to their resistance or susceptibility traits.
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影响因子：
4.5
作者：
Choi YJ;Bisset SA;Doyle SR;Hallsworth-Pepin K;Martin J;Grant WN;Mitreva M
通讯作者：
Mitreva M
Fasciola Hepatica表现出高水平的遗传多样性，缺乏种群结构和高基因流量：对耐药性的可能影响。
影响因子：
4
作者：
Beesley NJ;Williams DJ;Paterson S;Hodgkinson J
通讯作者：
Hodgkinson J
影响因子：
3.3
作者：
Doyle SR;Laing R;Bartley DJ;Britton C;Chaudhry U;Gilleard JS;Holroyd N;Mable BK;Maitland K;Morrison AA;Tait A;Tracey A;Berriman M;Devaney E;Cotton JA;Sargison ND
通讯作者：
Sargison ND
影响因子：
3.7
作者：
Charlier J;Hostens M;Jacobs J;Van Ranst B;Duchateau L;Vercruysse J
通讯作者：
Vercruysse J
影响因子：
2.4
作者：
HODASI, JKM
通讯作者：
HODASI, JKM