Biology subjects

Caccio, S. M.

Publications and source records attributed to Caccio, S. M..

5 recordsLinked to original sources

bioRxiv2026

An introgressed galectin-like protein is a candidate driver of the human tropism in the intestinal parasite Cryptosporidium

Cryptosporidium spp. are protozoan parasites responsible for diarrheal diseases. In humans, cryptosporidiosis is predominantly caused by the human-specific Cryptosporidium hominis and by Cryptosporidium parvum. This second species has been classically reported as zoonotic, with a host preference for ruminants. However, the recently described subspecies C. parvum anthroponosum has been found to be restricted to humans. Here, we generated novel whole genome sequences from West African samples of C. p. anthroponosum, and analyzed them together with all those already available, originating from East Africa, Europe, North America and Asia. Phylogenomics showed that all C. p. anthroponosum isolates are strongly clustered together, forming the sister clade of the zoonotic C. parvum representatives. The phylogenetic variations within C. p. anthroponosum did not present a clear geographic structure, consistent with C. hominis, primarily transmitted in humans. To elucidate the evolution of host species adaptation in C. p. anthroponosum, we then investigated genetic exchanges with C. hominis, detecting an ancestral introgression present in all C. p. anthroponosum isolates. This introgression involved a single gene, encoding for an extracellular galectin-like protein, which we predicted with high confidence to form a protein complex with the human insulin-degrading enzyme, a key metabolic regulator. Considering the role of host insulin metabolism in the proliferation of parasites as well as its known intrinsic differences between humans and ruminants, this molecular interaction could represent a plausible mechanism for an important role of the galectin-like protein in host-parasite interactions and in the host specificity of C. p. anthroponosum.

genomics↗

bioRxiv2023

Comparative genomics reveals the emergence of an outbreak-associated Cryptosporidium parvum population in Europe and its spread to the USA

The zoonotic parasite Cryptosporidium parvum is a global cause of gastrointestinal disease in humans and ruminants. Sequence analysis of the highly polymorphic gp60 gene enabled the classification of C. parvum isolates into multiple groups (e.g. IIa, IIc, Id) and a large number of subtypes. In Europe, subtype IIaA15G2R1 is largely predominant and has been associated with many water-and food-borne outbreaks. In this study, we generated new whole genome sequence (WGS) data from 123 human-and ruminant-derived isolates collected in 13 European countries and included other available WGS data from Europe, Egypt, China and the USA (n=72) in the largest comparative genomics study to date. We applied rigorous filters to exclude mixed infections and analysed a dataset from 141 isolates from the zoonotic groups IIa (n=119) and IId (n=22). Based on 28,047 high quality, biallelic genomic SNPs, we identified three distinct and strongly supported populations: isolates from China (IId) and Egypt (IIa and IId) formed population 1, a minority of European isolates (IIa and IId) formed population 2, while the majority of European (IIa, including all IIaA15G2R1 isolates) and all isolates from the USA (IIa) clustered in population 3. Based on analyses of the population structure, population genetics and recombination, we show that population 3 has recently emerged and expanded throughout Europe to then, possibly from the UK, reach the USA where it also expanded. In addition, genetic exchanges between different populations led to the formation of mosaic genomes. The reason(s) for the successful spread of population 3 remained elusive, although genes under selective pressure uniquely in this population were identified.

genomics↗

bioRxiv2021

VIVID: a web application for variant interpretation and visualisation in multidimensional analyses

Large-scale comparative genomics- and population genetic studies generate enormous amounts of polymorphism data in the form of DNA variants. Ultimately, the goal of many of these studies is to associate genetic variants to phenotypes or fitness. We introduce VIVID, an interactive, user-friendly web application that integrates a wide range of approaches for encoding genotypic to phenotypic information in any organism or disease, from an individual or population, in three-dimensional (3D) space. It allows mutation mapping and annotation, calculation of interactions and conservation scores, prediction of harmful effects, analysis of diversity and selection, and 3-dimensional (3D) visualisation of genotypic information encoded in Variant Call Format (VCF) on AlphaFold2 protein models. VIVID enables the rapid assessment of genes of interest in the study of adaptive evolution and the genetic load, and it helps prioritising targets for experimental validation. We demonstrate the utility of VIVID by exploring the evolutionary genetics of the parasitic protist Plasmodium falciparum, revealing geographic variation in the signature of balancing selection in potential targets of functional antibodies.

bioinformatics↗

bioRxiv2021

Evolutionary epidemiology of a zoonosis

Cryptosporidium parvum is a global zoonoses and a major cause of diarrhoea in humans and ruminants. The parasites life cycle comprises an obligatory sexual phase, during which genetic exchanges can occur between previously isolated lineages. Here, we compare 32 whole genome sequences from human- and ruminant-derived parasite isolates collected across Europe, Egypt and China. We identify three strongly supported clusters that comprise a mix of isolates from different host species, geographic origins, and subtypes. We show that: (1) recombination occurs between ruminant isolates into human isolates; (2) these recombinant regions can be passed on to other human subtypes through gene flow and population admixture; (3) there have been multiple genetic exchanges, and all are likely recent; (4) putative virulence genes are significantly enriched within these genetic exchanges, and (5) this results in an increase in their nucleotide diversity. We carefully dissect the phylogenetic sequence of two genetic exchanges, illustrating the long-term evolutionary consequences of these events. Our results suggest that increased globalisation and close human-animal contacts increase the opportunity for genetic exchanges between previously isolated parasite lineages, resulting in spillover and spillback events. We discuss how this can provide a novel substrate for natural selection at genes involved in host-parasite interactions, thereby potentially altering the dynamic coevolutionary equilibrium in the Red Queens arms race. Data SummaryAll raw and processed sequencing data generated and analysed during the current study have been submitted to the NCBI Sequence Read Archive (https://www.ncbi.nlm.nih.gov/bioproject/), under BioProjects PRJNA634014 and PRJNA633764.

evolutionary biology↗

bioRxiv2021

Population genomics of Cryptosporidium hominis across five continents identifies two subspecies that have diverged and recombined during 500 years of evolution

Cryptosporidiosis is a major global health problem and a primary cause of diarrhoea, particularly in young children in low- and middle-income countries (LMICs). The zoonotic Cryptosporidium parvum and anthroponotic C. hominis cause most human infections. Here, we present a comprehensive whole-genome study of C. hominis, comprising 114 isolates from 16 countries within five continents. We detect two lineages with distinct biology and demography, which diverged circa 500 years ago. We consider these lineages two subspecies and propose the names C. hominis hominis and C. hominis aquapotentis (gp60 subtype IbA10G2). In our study, C. h. hominis is almost exclusively represented by isolates from LMICs in Africa and Asia and appears to have undergone recent population contraction. In contrast, C. h. aquapotentis was found in high-income countries, mainly in Europe, North America and Oceania, and appears to be expanding. Notably, C. h. aquapotentis is associated with high rates of direct human-to-human transmission, which may explain its success in countries with well-developed environmental sanitation infrastructure. Intriguingly, we detected genomic regions of introgression following secondary contact between the subspecies. This resulted in high diversity and divergence in genomic islands of putative virulence genes (GIPVs), including muc5 (CHUDEA2_430) and a hypothetical protein (CHUDEA6_5270). This diversity is maintained by balancing selection, suggesting a coevolutionary arms race with the host. Lastly, we find that recent gene flow from C. h. aquapotentis to C. h. hominis, likely associated with increased human migration, may be driving evolution of more virulent C. hominis variants.

genomics↗