Dataset Information

Prevalence and Genotyping of Cryptosporidium parvum in Gastrointestinal Cancer Patients.

ABSTRACT: Gastrointestinal cancers are the most commonly occurring malignancies which contributing to over 1/5 of cancer incidences worldwide. Increasing evidences have shown that Cryptosporidium spp., an apicomplexan protozoan, is highly associated with gastrointestinal cancers. However, the prevalence of Cryptosporidium spp. infections among gastrointestinal cancer patients in China has not been estimated yet. We here performed a case-control study to evaluate the occurrences of Cryptosporidium spp. in patients with digestive malignancies before chemotherapy and in control population. Nested PCR amplifying 18S rRNA gene was used to detect the presence of Cryptosporidium spp. in each fecal sample. The results herein confirmed the correlation of Cryptosporidium spp. infection with colorectal and liver cancers, while first identified the high frequencies of Cryptosporidium spp. in esophageal cancer and small intestine cancer. The infection rates of Cryptosporidium spp. in colorectal, esophageal, liver and small intestine cancers were 17.24% (20/116, P<0.001), 6.25% (1/16, P=0.029), 14.29% (1/7, P<0.001) and 40% (2/5, P<0.001), respectively. In addition, molecular characterization indicated that all the Cryptosporidium spp. obtained were Cryptosporidium parvum (C. parvum), and the 18S rRNA sequences were identical to the reference sequences isolated from cattle, suggesting potential zoonotic transmission. Furthermore, subtyping analyses revealed that IIaA15G2R1 and IIaA15G2R2 were the predominant subtypes in colorectal cancer, while IIaA13G2R2 subtype was first named and identified in colorectal and liver cancers. Taken together, for the first time, the prevalence of Cryptosporidium spp. infections in digestive cancer patients has been estimated among Chinese. Our results indicated that C. parvum were highly associated with gastrointestinal cancers, supporting that cryptosporidiosis could be a potential risk factor for these diseases.

SUBMITTER: Zhang N

PROVIDER: S-EPMC7097938 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prevalence and Genotyping of Cryptosporidium parvum in Gastrointestinal Cancer Patients.

Zhang Nan N Yu Xiuyan X Zhang Hongbo H Cui Lianying L Li Xiaoou X Zhang Xiaowei X Gong Pengtao P Li Jianhua J Li Ziyi Z Wang Xiaocen X Li Xin X Li Ting T Liu Xiaofeng X Yu Yanhui Y Zhang Xichen X

Journal of Cancer 20200305 11

Gastrointestinal cancers are the most commonly occurring malignancies which contributing to over 1/5 of cancer incidences worldwide. Increasing evidences have shown that Cryptosporidium spp., an apicomplexan protozoan, is highly associated with gastrointestinal cancers. However, the prevalence of Cryptosporidium spp. infections among gastrointestinal cancer patients in China has not been estimated yet. We here performed a case-control study to evaluate the occurrences of Cryptos ...[more]

PMID: 32231739

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Project description:BackgroundHundreds of millions of people are infected with cryptosporidiosis annually, with immunocompromised individuals suffering debilitating symptoms and children in socioeconomically challenged regions at risk of repeated infections. There is currently no effective drug available. In order to facilitate the pursuit of anti-cryptosporidiosis targets and compounds, our study spans the classification of the Cryptosporidium parvum kinome and the structural and biochemical characterization of representatives from the CDPK family and a MAP kinase.ResultsThe C. parvum kinome comprises over 70 members, some of which may be promising drug targets. These C. parvum protein kinases include members in the AGC, Atypical, CaMK, CK1, CMGC, and TKL groups; however, almost 35% could only be classified as OPK (other protein kinases). In addition, about 25% of the kinases identified did not have any known orthologues outside of Cryptosporidium spp. Comparison of specific kinases with their Plasmodium falciparum and Toxoplasma gondii orthologues revealed some distinct characteristics within the C. parvum kinome, including potential targets and opportunities for drug design. Structural and biochemical analysis of 4 representatives of the CaMK group and a MAP kinase confirms features that may be exploited in inhibitor design. Indeed, screening CpCDPK1 against a library of kinase inhibitors yielded a set of the pyrazolopyrimidine derivatives (PP1-derivatives) with IC₅₀ values of < 10 nM. The binding of a PP1-derivative is further described by an inhibitor-bound crystal structure of CpCDPK1. In addition, structural analysis of CpCDPK4 identified an unprecedented Zn-finger within the CDPK kinase domain that may have implications for its regulation.ConclusionsIdentification and comparison of the C. parvum protein kinases against other parasitic kinases shows how orthologue- and family-based research can be used to facilitate characterization of promising drug targets and the search for new drugs.

Project description:There is a need for an integrated genotyping approach for C. parvum; no sufficiently discriminatory scheme to date has been fully validated or widely adopted by veterinary or public health researchers. Multilocus fragment typing (MLFT) can provide good differentiation and is relatively quick and cheap to perform. A MLFT tool was assessed in terms of its typeability, specificity, precision (repeatability and reproducibility), accuracy and ability to genotypically discriminate bovine-derived Cryptosporidium parvum.With the aim of working towards a consensus, six markers were selected for inclusion based on their successful application in previous studies: MM5, MM18, MM19, TP14, MS1 and MS9. Alleles were assigned according to the fragment sizes of repeat regions amplified, as determined by capillary electrophoresis. In addition, a region of the GP60 gene was amplified and sequenced to determine gp60 subtype and this was added to the allelic profiles of the 6 markers to determine the multilocus genotype (MLG). The MLFT tool was applied to 140 C. parvum samples collected in two cross-sectional studies of UK calves, conducted in Cheshire in 2004 (principally dairy animals) and Aberdeenshire/Caithness in 2011 (beef animals).Typeability was 84 %. The primers did not amplify tested non-parvum species frequently detected in cattle. In terms of repeatability, within- and between-run fragment sizes showed little variability. Between laboratories, fragment sizes differed but allele calling was reproducible. The MLFT had good discriminatory ability (Simpson's Index of Diversity, SID, was 0.92), compared to gp60 sequencing alone (SID 0.44). Some markers were more informative than others, with MS1 and MS9 proving monoallelic in tested samples.Further inter-laboratory trials are now warranted with the inclusion of human-derived C. parvum samples, allowing progress towards an integrated, standardised typing scheme to enable source attribution and to determine the role of livestock in future outbreaks of human C. parvum.

Dataset Information

Prevalence and Genotyping of Cryptosporidium parvum in Gastrointestinal Cancer Patients.

Publications

Prevalence and Genotyping of <i>Cryptosporidium parvum</i> in Gastrointestinal Cancer Patients.

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