Shaw Sebastian, Li Xue, Buenconsejo Gracyn, Zhou Tiffany H, Cohen Allison, Yasur-Landau Daniel, Xiao Rui, Beiting Daniel P, Anderson Timothy J C, Striepen Boris
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Texas Biomedical Research Institute, San Antonio, Texas, USA.
bioRxiv. 2025 May 21:2025.05.20.655157. doi: 10.1101/2025.05.20.655157.
The relationship between parasite genotype and pathogenesis is largely unknown for , a leading cause of diarrheal disease in children. An array of parasites with similar genomes produces varied disease outcomes in different hosts. Here, we isolate and characterize strains that show marked differences in virulence and persistence in mice. Taking advantage of the sexual lifecycle of this eukaryotic pathogen, we use genetic crosses to discover the underlying chromosomal loci. Whole-genome sequencing and bulk segregant analysis of infection selected progeny mapped three loci on chromosomes 2, 6, and 7 associated with the ability to colonize and persist in mice and the positions of drug resistance genes. The chromosome 6 locus encodes the hyper-polymorphic surface glycoprotein GP60. Reverse genetic studies in both parental strains demonstrate that GP60 controls parasite burden and virulence, but not persistence, and reveal the dominance of the less virulent allele, suggesting it restricts virulence.
作为儿童腹泻病的主要病因，寄生虫基因型与发病机制之间的关系在很大程度上尚不清楚。一系列具有相似基因组的寄生虫在不同宿主中产生不同的疾病结果。在这里，我们分离并鉴定了在小鼠体内毒力和持久性表现出显著差异的菌株。利用这种真核病原体的有性生命周期，我们通过遗传杂交来发现潜在的染色体位点。对感染选定后代进行全基因组测序和群体分离分析，在2号、6号和7号染色体上定位了三个与在小鼠体内定殖和持续存在能力以及耐药基因位置相关的位点。6号染色体位点编码高度多态的表面糖蛋白GP60。对两个亲本菌株进行的反向遗传学研究表明，GP60控制寄生虫负荷和毒力，但不控制持久性，并揭示了低毒力等位基因的显性，表明它限制了毒力。
