Glycoproteins and Gal-GalNAc cause Cryptosporidium to switch from an invasive sporozoite to a replicative trophozoite.

The apicomplexan parasite Cryptosporidium causes cryptosporidiosis, a diarrheal disease that can become chronic and life threatening in immunocompromised and malnourished people. There is no effective drug treatment for those most at risk of severe cryptosporidiosis. The disease pathology is due to a repeated cycle of host cell invasion and parasite replication that amplifies parasite numbers and destroys the intestinal epithelium. This study aimed to better understand the Cryptosporidium replication cycle by identifying molecules that trigger the switch from invasive sporozoite to replicative trophozoite. Our approach was to treat sporozoites of Cryptosporidium parvum and Cryptosporidium hominis, the species causing most human cryptosporidiosis, with various media under axenic conditions and examine the parasites for rounding and nuclear division as markers of trophozoite development and replication, respectively. FBS had a concentration-dependent effect on trophozoite development in both species. Trophozoite development in C. parvum, but not C. hominis, was enhanced when RPMI supplemented with 10% FBS (RPMI-FBS) was conditioned by HCT-8 cells for 3h. The effect of non-conditioned and HCT-8 conditioned RPMI-FBS on trophozoite development was abrogated by proteinase K and sodium metaperiodate pretreatment, indicating a glycoprotein trigger. Cryptosporidium parvum and C. hominis trophozoite development also was triggered by Gal-GalNAc in a concentration-dependent manner. Cryptosporidium parvum replication was greatest following treatments with Gal-GalNAc, followed by conditioned RPMI-FBS and non-conditioned RPMI-FBS (P<0.05). Cryptosporidium hominis replication was significantly less than that in C. parvum for all treatments (P<0.05), and was greatest at the highest tested concentration of Gal-GalNAc (1mM).

Edwinson A ，Widmer G ，McEvoy J 《-》

Mechanisms of attachment and internalization of Cryptosporidium parvum to biliary and intestinal epithelial cells.

Chen XM ，LaRusso NF 《GASTROENTEROLOGY》

Cryptosporidium p30, a galactose/N-acetylgalactosamine-specific lectin, mediates infection in vitro.

Bhat N ，Joe A ，PereiraPerrin M ，Ward HD ... -  《JOURNAL OF BIOLOGICAL CHEMISTRY》

Interaction of Cryptosporidium hominis and Cryptosporidium parvum with primary human and bovine intestinal cells.

Hashim A ，Mulcahy G ，Bourke B ，Clyne M ... -  《-》

Cryptic parasite revealed improved prospects for treatment and control of human cryptosporidiosis through advanced technologies.

Cryptosporidium is an important genus of parasitic protozoa of humans and other vertebrates and is a major cause of intestinal disease globally. Unlike many common causes of infectious enteritis, there are no widely available, effective vaccine or drug-based intervention strategies for Cryptosporidium, and control is focused mainly on prevention. This approach is particularly deficient for infections of severely immunocompromised and/or suppressed, the elderly or malnourished people. However, cryptosporidiosis also presents a significant burden on immunocompetent individuals, and can, for example have lasting effects on the physical and mental development of children infected at an early age. In the last few decades, our understanding of Cryptosporidium has expanded significantly in numerous areas, including the parasite life-cycle, the processes of excystation, cellular invasion and reproduction, and the interplay between parasite and host. Nonetheless, despite extensive research, many aspects of the biology of Cryptosporidium remain unknown, and treatment and control are challenging. Here, we review the current state of knowledge of Cryptosporidium, with a focus on major advances arising from the recently completed genome sequences of the two species of greatest relevance in humans, namely Cryptosporidium hominis and Cryptosporidium parvum. In addition, we discuss the potential of next-generation sequencing technologies, new advances in in silico analyses and progress in in vitro culturing systems to bridge these gaps and to lead toward effective treatment and control of cryptosporidiosis.

Jex AR ，Smith HV ，Nolan MJ ，Campbell BE ，Young ND ，Cantacessi C ，Gasser RB ... -  《-》