Diverse single-amino-acid repeat profiles in the genusCryptosporidium

Abstract

Genome sequencing has greatly contributed to our understanding of parasitic protozoa. This is particularly the case for Cryptosporidium species (phylum Apicomplexa) which are difficult to propagate. Because of their polymorphic nature, simple sequence repeats have been used extensively as genotypic markers to differentiate between isolates, but no global analysis of amino acid repeats in Cryptosporidium genomes has been reported. Taking advantage of several newly sequenced Cryptosporidium genomes, a comparative analysis of single-amino-acid repeats (SAARs) in seven species was undertaken. This analysis revealed a striking difference between the SAAR profile of the gastric and intestinal species which infect mammals and one species which infects birds. In average, total SAAR length in gastric species is only 25% of the cumulative SAAR length in the genome of Cryptosporidium parvum, Cryptosporidium hominis and Cryptosporidium meleagridis, species infectious to humans. The SAAR profile in the avian parasite Cryptosporidium baileyi stands out due to the presence of long asparagine repeats. Cryptosporidium baileyi proteins with repeats ⩾20 residues are significantly enriched in regulatory functions. As postulated for the related apicomplexan species Plasmodium falciparum, these observations suggest that Cryptosporidium SAARs evolve in response to selective pressure. The putative selective mechanisms driving SAAR evolution in Cryptosporidium species are unknown.

Comparative genomic analysis of the principal Cryptosporidium species that infect humans

“…Mutated genes annotated in our study also code for surface proteins with transmembrane domains and proteins secreted by non-classical pathways, suggesting that the interaction processes between the parasite and the host cells could be affected. This finding agrees with that reported by other authors who have described that the processes that are mainly affected are adhesion and invasion ( Li et al, 2013 ; Isaza et al, 2015 ; Gilchrist et al, 2018 ; Widmer, 2018 ; Xu et al, 2019 ). It has been determined that the proteins secreted by non-classical pathways usually are growth factors, inflammatory cytokines, components of the extracellular matrix that regulate cell differentiation, proliferation, and apoptosis, as well as surface proteins in parasites involved in the initial interaction with the host ( Nickel, 2003 ).…”

Peer Review #2 of "Comparative genomic analysis of the principal Cryptosporidium species that infect humans (v0.1)"

“…Mutated genes annotated in our study also code for surface proteins with transmembrane domains and proteins secreted by non-classical pathways, suggesting that the interaction processes between the parasite and the host cells could be affected. This finding agrees with that reported by other authors who have described that the processes that are mainly affected are adhesion and invasion (Li et al, 2013;Isaza et al, 2015;Gilchrist et al, 2018;Widmer, 2018;Xu et al, 2019). It has been determined that the proteins secreted by non-classical pathways usually are growth factors, inflammatory cytokines, components of the extracellular matrix that regulate cell differentiation, proliferation, and apoptosis, as well as surface proteins in parasites involved in the initial interaction with the host (Nickel, 2003).…”

State of the Art and Future Directions ofCryptosporidiumspp.

“…No fully effective drug therapy or vaccine is available for Cryptosporidium, and the diagnosis of cryptosporidiosis has been based on the demonstration of oocysts in faeces, which present low sensibility [25]. However, the ability to culture relevant Cryptosporidium isolates in vitro, the development of novel gene-editing tools (knockout genes, CRISPR/ Cas9, and RNAi) [26][27][28][29][30], and 'omic' research (genomics, transcriptomics, and proteomics) represent essential paths towards significant advancements in the control of cryptosporidiosis [30][31][32][33][34][35][36][37][38]. In the future, those approaches will show a holistic view of the biology of Cryptosporidium.…”