Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Trends Parasitol. 2022 Aug;38(8):618-628. doi: 10.1016/j.pt.2022.05.005. Epub 2022 May 28.
The conserved plasmodial surface anion channel (PSAC) mediates nutrient uptake by bloodstream malaria parasites and is an antimalarial target. This pathogen-associated channel is linked to the clag multigene family, which is variably expanded in Plasmodium spp. Member genes are under complex epigenetic regulation, with the clag3 genes of the human P. falciparum pathogen exhibiting monoallelic transcription and mutually exclusive surface exposure on infected erythrocytes. While other multigene families use monoallelic expression to evade host immunity, the reasons of epigenetic control of clag genes are unclear. I consider existing models and their implications for nutrient acquisition and immune evasion. Understanding the reasons for epigenetic regulation of PSAC-mediated nutrient uptake will help clarify host-pathogen interactions and guide development of therapies resistant to allele switching.
保守的疟原虫表面阴离子通道 (PSAC) 介导血疟原虫对营养物质的摄取,是一种抗疟靶点。这种病原体相关的通道与 clag 多基因家族有关,该家族在疟原虫属中存在可变扩展。成员基因受到复杂的表观遗传调控,人类疟原虫病原体的 clag3 基因表现出单等位基因转录和受感染红细胞上的相互排斥的表面暴露。虽然其他多基因家族利用单等位基因表达来逃避宿主免疫,但 clag 基因的表观遗传控制的原因尚不清楚。我考虑了现有的模型及其对营养物质获取和免疫逃避的影响。了解 PSAC 介导的营养摄取的表观遗传调控的原因将有助于阐明宿主-病原体相互作用,并指导开发抗等位基因转换的治疗方法。