Plasmodium falciparum ring-stage plasticity and drug resistance.

Plasmodium falciparum has evolved resistance to almost all antimalarial drugs through genomic changes –SNPs and copy number variants (CNVs) – and a nonspecific stress-response-based survival such as the ring-stage temporary growth arrest (TGA). The ring-stage can develop into asexual or sexual stages or stop growing when conditions are unfavorable. The ring-stage shows extreme plasticity under adverse conditions, such as artemisinin exposure. The ring-stage TGA stage exhibits an innate and passive resistance to many stressors, which ensures that some individuals in the population can survive in the host. P. falciparum ring-stage TGA may rely on environmental sensing and extracellular communication between the parasites. Ring-stage TGA may be an underestimated parasite reservoir, especially in asymptomatic individuals. No treatment that specifically targets growth-arrested ring stages is currently available. Malaria is a life-threatening tropical disease caused by parasites of the genus Plasmodium, of which Plasmodium falciparum is the most lethal. Malaria parasites have a complex life cycle, with stages occurring in both the Anopheles mosquito vector and human host. Ring stages are the youngest form of the parasite in the intraerythrocytic developmental cycle and are associated with evasion of spleen clearance, temporary growth arrest (TGA), and drug resistance. This formidable ability to survive and develop into mature, sexual, or growth-arrested forms demonstrates the inherent population heterogeneity. Here we highlight the role of the ring stage as a crossroads in parasite development and as a reservoir of surviving cells in the human host via TGA survival mechanisms. [ABSTRACT FROM AUTHOR]