Abstract
Cryptosporidium parvum is known to cause life-threatening diarrhea in immunocompromised hosts and was also reported to be capable of inducing digestive adenocarcinoma in a rodent model. Interestingly, three carcinogenic isolates of C. parvum, called DID, TUM1 and CHR, obtained from fecal samples of naturally infected animals or humans, showed higher virulence than the commercially available C. parvum IOWA isolate in our animal model in terms of clinical manifestations, mortality rate and time of onset of neoplastic lesions. In order to discover the potential genetic basis of the differential virulence observed between C. parvum isolates and to contribute to the understanding of Cryptosporidium virulence, entire genomes of the isolates DID, TUM1 and CHR were sequenced then compared to the C. parvum IOWA reference genome. 125 common SNVs corresponding to 90 CDSs were found in the C. parvum genome that could explain this differential virulence. In particular variants in several membrane and secreted proteins were identified. Besides the genes already known to be involved in parasite virulence, this study identified potential new virulence factors whose functional characterization can be achieved through CRISPR/Cas9 technology applied to this parasite.
Highlights
Cryptosporidium parvum is known to cause life-threatening diarrhea in immunocompromised hosts and was reported to be capable of inducing digestive adenocarcinoma in a rodent model
The post-infection mortality rate at 60 days for mice inoculated with TUM1, DID and CHR isolates was 29, 41 and 29% respectively, while mice inoculated with C. parvum IOWA were all alive at this time (Table 1)
In this study the genomes of three highly virulent C. parvum isolates isolated from fecal samples of naturally infected animals or humans and reported to induce digestive adenocarcinoma in a rodent model[17,18,19,20,21], were sequenced and compared with the reference genome C. parvum IOWA5
Summary
Cryptosporidium parvum is known to cause life-threatening diarrhea in immunocompromised hosts and was reported to be capable of inducing digestive adenocarcinoma in a rodent model. Cryptosporidium apicomplexan parasites represent a major public health problem in humans and animals causing self-limited diarrhea in immunocompetent hosts and life-threatening disease in immunocompromised hosts, for which efficient drug therapy is still lacking. Human is the major host for C. hominis while C. parvum is frequently reported both in humans and animals, in bovids[4]. The genomes of laboratory isolates of C. parvum IOWA5, C. hominis (TU502)[6], and C. muris (RN66) (published in online public databases, e.g., CryptoDB http://cryptodb.org) were reported a decade ago.
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