Forward Genetics in Apicomplexa Biology: The Host Side of the Story.

Forward genetic approaches have been widely used in parasitology and have proven their power to reveal the complexities of host-parasite interactions in an unbiased fashion. Many aspects of the parasite’s biology, including the identification of virulence factors, replication determinants, antibiotic resistance genes, and other factors required for parasitic life, have been discovered using such strategies. Forward genetic approaches have also been employed to understand host resistance mechanisms to parasitic infection. Here, we will introduce and review all forward genetic approaches that have been used to identify host factors involved with Apicomplexa infections, which include classical genetic screens and QTL mapping, GWAS, ENU mutagenesis, overexpression, RNAi and CRISPR-Cas9 library screens. Collectively, these screens have improved our understanding of host resistance mechanisms, immune regulation, vaccine and drug designs for Apicomplexa parasites. We will also discuss how recent advances in molecular genetics give present opportunities to further explore host-parasite relationships.

正向遗传学方法已在寄生虫学中广泛应用，并已证明其能够以无偏见的方式揭示宿主 - 寄生虫相互作用的复杂性。利用这些策略，已经发现了寄生虫生物学的许多方面，包括毒力因子的鉴定、复制决定因素、抗生素抗性基因以及寄生生活所需的其他因素。正向遗传学方法也被用于了解宿主对寄生虫感染的抗性机制。在此，我们将介绍和综述所有用于鉴定与顶复门寄生虫感染相关的宿主因子的正向遗传学方法，包括经典遗传筛选和数量性状基因座（QTL）定位、全基因组关联研究（GWAS）、N - 乙基 - N - 亚硝基脲（ENU）诱变、过表达、RNA干扰（RNAi）以及CRISPR - Cas9文库筛选。总体而言，这些筛选提高了我们对顶复门寄生虫的宿主抗性机制、免疫调节、疫苗和药物设计的理解。我们还将讨论分子遗传学的最新进展如何为进一步探索宿主 - 寄生虫关系提供当前的机遇。