Past and future trends of Cryptosporidium in vitro research

Abstract

Cryptosporidium is a genus of single celled parasites capable of infecting a wide range of animals including humans. Cryptosporidium species are members of the phylum apicomplexa, which includes well-known genera such as Plasmodium and Toxoplasma. Cryptosporidium parasites cause a severe gastro-intestinal disease known as cryptosporidiosis. They are one of the most common causes of childhood diarrhoea worldwide, and infection can have prolonged detrimental effects on the development of children, but also can be life threatening to HIV/AIDS patients and transplant recipients. A variety of hosts can act as reservoirs, and Cryptosporidium can persist in the environment for prolonged times as oocysts. While there has been substantial interest in these parasites, there is very little progress in terms of treatment development and understanding the majority of the life cycle of this unusual organism. In this review, we will provide an overview on the existing knowledge of the biology of the parasite and the current progress in developing in vitro cultivation systems. We will then describe a synopsis of current and next generation approaches that could spearhead further research in combating the parasite.

Fig. 1

Outline of the Cryptosporidium parvum life cycle [Adapted and modified from (Thompson et al., 2005)]. Ingested oocysts release sporozoites, which invade the ileum, developing into trophozoites and type I meronts, containing type I merozoites. Released type I Merozoites can become trophozoites themselves or develop into type II meronts, which release type II merozoites, these develop into undifferentiated gamonts. Gamonts differentiate into macrogamonts or microgamonts, the latter produces microgametes, which fertilise macrogamonts. Sporulation occurs within the host, releasing thick walled oocysts into the environment and thin walled oocysts, which auto-infect the same host organism.

Fig. 2

Organelles in C. parvum infection. Transmission Electron Microscopy (TEM) images showing the presence of a feeder organelle and mitochondrial-related organelles that are formed within the parasite infecting COLO-680N cells. a. TEM image showing the formation of the feeder organelle (fo), which anchors the main body of the parasite to the peripheral of the parasitophorous vacuole (pv). b. TEM image demonstrating a clearly identifiable double membrane structure of the mitosome within a merozoite form of C. parvum. c. TEM image showing numerous organelles within the sporozoite that has recently invaded a host cell. The electron dense structure that can be seen is the crystalloid body (cb). The nucleus (nuc) and the mitosome (ms) can also be seen in this image.