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Comparative genomic analysis of the principal Cryptosporidium species that infect humans.

ABSTRACT: Cryptosporidium parasites are ubiquitous and can infect a broad range of vertebrates and are considered the most frequent protozoa associated with waterborne parasitic outbreaks. The intestine is the target of three of the species most frequently found in humans: C. hominis, C. parvum, and. C. meleagridis. Despite the recent advance in genome sequencing projects for this apicomplexan, a broad genomic comparison including the three species most prevalent in humans have not been published so far. In this work, we downloaded raw NGS data, assembled it under normalized conditions, and compared 23 publicly available genomes of C. hominis, C. parvum, and C. meleagridis. Although few genomes showed highly fragmented assemblies, most of them had less than 500 scaffolds and mean coverage that ranged between 35X and 511X. Synonymous single nucleotide variants were the most common in C. hominis and C. meleagridis, while in C. parvum, they accounted for around 50% of the SNV observed. Furthermore, deleterious nucleotide substitutions common to all three species were more common in genes associated with DNA repair, recombination, and chromosome-associated proteins. Indel events were observed in the 23 studied isolates that spanned up to 500 bases. The highest number of deletions was observed in C. meleagridis, followed by C. hominis, with more than 60 species-specific deletions found in some isolates of these two species. Although several genes with indel events have been partially annotated, most of them remain to encode uncharacterized proteins.

SUBMITTER: Arias-Agudelo LM

PROVIDER: S-EPMC7718795 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comparative genomic analysis of the principal Cryptosporidium species that infect humans.

Arias-Agudelo Laura M LM Garcia-Montoya Gisela G Cabarcas Felipe F Galvan-Diaz Ana L AL Alzate Juan F JF

PeerJ 20201202

Cryptosporidium parasites are ubiquitous and can infect a broad range of vertebrates and are considered the most frequent protozoa associated with waterborne parasitic outbreaks. The intestine is the target of three of the species most frequently found in humans: C. hominis, C. parvum, and. C. meleagridis. Despite the recent advance in genome sequencing projects for this apicomplexan, a broad genomic comparison including the three species most prevalent in humans have ...[more]

PMID: 33344091

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Project description:The three common intestinal Cryptosporidium species in cattle differ significantly in host range, pathogenicity and public health significance. While Cryptosporidium parvum is pathogenic in pre-weaned calves and has a broad host range, C. bovis and C. ryanae are largely non-pathogenic and bovine-specific species in post-weaned calves. Thus far, only the genome of C. parvum has been sequenced. To improve our understanding of the genetic determinants of biological differences among Cryptosporidium spcies, we sequenced the genomes of C. bovis and C. ryanae and conducted a comparative genomics analysis. The genome of C. bovis has a gene content and organization more similar to C. ryanae than to other Cryptosporidium species sequenced to date; the level of similarity in amino acid and nucleotide sequences between the two species is 75.2 and 69.4 %, respectively. A total of 3723 and 3711 putative protein-encoding genes were identified in the genomes of C. bovis and C. ryanae, respectively, which are fewer than the 3981 in C. parvum. Metabolism is similar among the three species, although energy production pathways are further reduced in C. bovis and C. ryanae. Compared with C. parvum, C. bovis and C. ryanae have lost 14 genes encoding mucin-type glycoproteins and three for insulinase-like proteases. Other gene gains and losses in the two bovine-specific and non-pathogenic species also involve the secretory pathogenesis determinants (SPDs); they have lost all genes encoding MEDLE, FLGN and SKSR proteins, and two of the three genes for NFDQ proteins, but have more genes encoding secreted WYLE proteins, secreted leucine-rich proteins and GPI-anchored adhesin PGA18. The only major difference between C. bovis and C. ryanae is in nucleotide metabolism. In addition, half of the highly divergent genes between C. bovis and C. ryanae encode secreted or membrane-bound proteins. Therefore, C. bovis and C. ryanae have gene organization and metabolic pathways similar to C. parvum, but have lost some invasion-associated mucin glycoproteins, insulinase-like proteases, MEDLE secretory proteins and other SPDs. The multiple gene families under positive selection, such as helicase-associated domains, AMP-binding domains, protein kinases, mucins, insulinases and TRAPs could contribute to differences in host specificity and pathogenicity between C. parvum and C. bovis. Biological studies should be conducted to assess the contribution of these copy number variations to the narrow host range and reduced pathogenicity of C. bovis and C. ryanae.

Project description:AbstractThe epidemiology of cryptosporidiosis in southern Africa is largely unknown. The disease is associated with diarrhea and nutritional deficiencies, leading to severe morbidity and mortality among immune-compromised patients. This study aimed to assess the pooled prevalence of Cryptosporidium spp. infection among immune-compromised humans in southern Africa over the past 20 years. Reports of Cryptosporidium spp. infection in humans published between 2000 and 2020 using Google Scholar, PubMed, Ovid Medline, African Journal Online (AJOL), and Web of Science literature databases were obtained. Inclusion criteria of sorted articles for Cryptosporidium spp. infection were standardized using preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. A total of 22 eligible studies were sorted for meta-analysis. Overall prevalence of Cryptosporidium spp. infection in southern African countries with reports was 16.8% (95% CI 9.7-25.3). Sub-group analysis showed a pooled prevalence of 25.2, 20.5, and 17.9% among HIV/AIDS patients, children, and diarrhoeic individuals, respectively. Pooled prevalence was highest in South Africa and lowest in Zimbabwe across examined individuals. The pooled prevalence of Cryptosporidium spp. infections in diarrhoeic patients was highest in individuals from Botswana (17.6%) which is significantly different (Χ 2 = 9.337; P = 0.002) from South Africans (12.7%). South African individuals with HIV/AIDS showed the highest pooled prevalence of Cryptosporidium infections than other countries. The high prevalence of Cryptosporidium spp. infections among immune-compromised patients in southern Africa showed that the pathogen is of significant importance in this region. Continuous studies on the genetic characterization of Cryptosporidium spp. isolates and associated risk factors are needed across southern Africa to identify the predominant subtypes in humans.Graphic abstractSupplementary informationThe online version contains supplementary material available at 10.1007/s12639-021-01436-4.

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Comparative genomic analysis of the principal Cryptosporidium species that infect humans.

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Comparative genomic analysis of the principal <i>Cryptosporidium</i> species that infect humans.

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