Abstract

Malaria parasites replicate inside erythrocytes of the host organism. Although this is a relatively safe haven from the host’s immune system, it exposes the parasite to potential removal of the infected erythrocyte in the spleen, where small, old and damaged erythrocytes are removed from the circulation. Late-stage parasites are large and ultimately take up ~75% of the cytosol of the erythrocyte and erythrocytes containing these large late-stage malaria parasites are rapidly removed from the blood circulation. In contrast, early-stage parasites are much smaller and erythrocytes containing these forms of the parasite are readily detected in the blood of an infected individual. Although the invasive merozoite form of the parasite is small and nearly spherical, inside the erythrocyte early-stage parasites assume very motile amoeboid shapes, with limbs that move, retract and extend again. Hence, the early-stage intracellular parasites have little resemblance to the invasive form of the parasite. However, how, when and why the parasite undergoes this shape change has been studied very little. To understand this remarkable transformation of merozoites to the intracellular amoeboid shape, we investigated the when, how and why of this process and discovered that it is rapid, likely very complex and involves the host’s spleen. Our results indicate that rather than passively settling into the host erythrocyte after invasion, the parasite undergoes a radical metamorphosis to increase its survival in the host.