School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK.
School of Natural Sciences, Bangor University, Deiniol Road, Bangor, Gwynedd LL57 2UW, UK.
Int J Parasitol. 2022 Jul;52(8):509-518. doi: 10.1016/j.ijpara.2022.04.001. Epub 2022 May 6.
Parasites, similar to all other organisms, time themselves to environmental cues using a molecular clock to generate and maintain rhythms. Chronotherapeutic (timed treatment) techniques based on such rhythms offer great potential for improving control of chronic, problematic parasites. Fish lice are a key disease threat in aquaculture, with current control insufficient. Assessing the rhythmicity of fish lice transcriptomes offers not only insight into the viability of chronotherapy, but the opportunity to identify new drug targets. Here, for the first known time in any crustacean parasite, diel changes in gene transcription are examined, revealing that approximately half of the Argulus foliaceus annotated transcriptome displays significant daily rhythmicity. We identified rhythmically transcribed putative clock genes including core clock/cycle and period/timeless pairs, alongside rhythms in feeding-associated genes and processes involving immune response, as well as fish louse drug targets. A substantial number of gene pathways showed peak transcription in hours immediately preceding onset of light, potentially in anticipation of peak host anti-parasite responses or in preparation for increased feeding activity. Genes related to immune haemocyte activity and chitin development were more highly transcribed 4 h post light onset, although inflammatory gene transcription was highest during dark periods. Our study provides an important resource for application of chronotherapy in fish lice; timed application could increase efficacy and/or reduce dose requirement, improving the current landscape of drug resistance and fish health while reducing the economic cost of infection.
寄生虫与所有其他生物一样,使用分子钟来感知环境线索,从而产生和维持节律。基于这些节律的chronotherapeutic(定时治疗)技术为改善对慢性、有问题的寄生虫的控制提供了巨大的潜力。鱼类虱子是水产养殖中的一个关键疾病威胁,目前的控制措施还不够。评估鱼类虱子转录组的节律性不仅提供了chronotherapy 可行性的见解,还为识别新的药物靶点提供了机会。在这里,首次在任何甲壳类寄生虫中检查了昼夜变化的基因转录,结果表明,大约有一半的三叶虫 annotated 转录组显示出显著的日常节律性。我们鉴定了节律性转录的假定生物钟基因,包括核心时钟/周期和周期/无时间对,以及与摄食相关的基因和涉及免疫反应的过程的节律,以及鱼类虱子的药物靶点。大量基因途径在光照开始前的几个小时内显示出转录高峰,可能是为了预测宿主抗寄生虫反应的高峰,或者是为了准备增加摄食活动。与免疫血球活动和几丁质发育相关的基因在光照后 4 小时转录水平更高,尽管在黑暗时期炎症基因的转录水平更高。我们的研究为在鱼类虱子中应用 chronotherapy 提供了重要的资源;定时应用可以提高疗效和/或降低剂量需求,改善当前的耐药性和鱼类健康状况,同时降低感染的经济成本。