Cryptosporidium pathogenicity and virulence – the parasite, the host, and the microbiome

The virulence of a pathogen varies from infection to infection. Cryptosporidium causes more diarrheal disease in humans and livestock than any other pathogen. Cryptosporidiosis is associated with serious illness, wasting and even death in some, but is asymptomatic in others. Host immunity and prior exposure are important factors, but do not explain the considerable variation observed between individuals on first exposure. As an enteric infection, virulence is believed to vary as a function of the interplay between parasite and host genetics and the composition of the enteric microbiota where infection occurs, with a proportion of the observed pathology attributable not just to damage by the parasite but by opportunistic bacteria colonizing the damaged tissue and immunopathology from the inflammatory response generated. In the past couple years, the Tyler group at the Norwich Medical School has demonstrated the significance of Cryptosporidium genotype in the transmission of disease. We hypothesize that this reflects the ability of those genotypes to colonize the host and thus the magnitude of damage to the enteric mucosa; that such damage can dramatically impact the composition of the enteric microbiota and that the resulting dysbiosis drives further damage and more severe disease in some parasite genotypes. This studentship will build on the opportunities established in those studies to characterise the relationship between specific virulent and avirulent genotypes and the expression of lineage specific virulence alleles with the genesis of enteric dysbiosis in livestock and humans and will specifically examine the causality of microbiome composition in exacerbation and attenuation of cryptosporidiosis. The studentship is a “one health” multidisciplinary project and will utilize genomic and in vitro methods to evaluate the role of parasite, host and microbiome in disease.