Dataset Information

Divergent Copies of a Cryptosporidium parvum-Specific Subtelomeric Gene.

ABSTRACT: Subtype families of Cryptosporidium parvum differ in host range, with IIa and IId being found in a broad range of animals, IIc in humans, and IIo and IIp in some rodents. Previous studies indicated that the subtelomeric cgd6_5520-5510 gene in C. parvum is lost in many Cryptosporidium species, and could potentially contribute to the broad host range of the former. In this study, we identified the presence of a second copy of the gene in some C. parvum subtype families with a broad host range, and showed sequence differences among them. The sequence differences in the cgd6_5520-5510 gene were not segregated by the sequence type of the 60 kDa glycoprotein gene. Genetic recombination appeared to have played a role in generating divergent nucleotide sequences between copies and among subtype families. These data support the previous conclusion on the potential involvement of the insulinase-like protease encoded by the subtelomeric cgd6_5520-5510 gene in the broad host range of C. parvum IIa and IId subtypes.

SUBMITTER: Zhang S

PROVIDER: S-EPMC6780254 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Divergent Copies of a Cryptosporidium parvum-Specific Subtelomeric Gene.

Zhang Shijing S Chen Li L Li Falei F Li Na N Feng Yaoyu Y Xiao Lihua L

Microorganisms 20190918 9

Subtype families of Cryptosporidium parvum differ in host range, with IIa and IId being found in a broad range of animals, IIc in humans, and IIo and IIp in some rodents. Previous studies indicated that the subtelomeric cgd6_5520-5510 gene in C. parvum is lost in many Cryptosporidium species, and could potentially contribute to the broad host range of the former. In this study, we identified the presence of a second copy of the gene in some C. parvum< ...[more]

PMID: 31540508

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Project description:BACKGROUND:Bamboo rats are widely farmed in southern China for meat, but their potential in transmitting pathogens to humans and other farm animals remains unclear. METHODS:To understand the transmission of Cryptosporidium spp. in these animals, 709 fecal samples were collected in this study from Chinese bamboo rats (Rhizomys sinensis) on nine farms in Jiangxi, Guangxi and Hainan provinces, China. They were analyzed for Cryptosporidium spp. using PCR and sequence analyses of the small subunit rRNA gene. Cryptosporidium parvum, C. parvum-like and C. ubiquitum-like genotypes identified were subtyped by sequence analysis of the 60 kDa glycoprotein (gp60) gene. RESULTS:Altogether, Cryptosporidium spp. were detected in 209 (29.5%) samples. The detection rate in samples from animals under two months of age (70.0%,105/150) was significantly higher than in samples from animals above 2 months (18.6%, 104/559; ?2?=?150.27, df?=?1, P?<?0.0001). Four Cryptosporidium species/genotypes were identified: C. parvum (n?=?78); C. occultus (n?=?1); a new genotype that is genetically related to C. ubiquitum (n?=?85); and another new genotype that is genetically related to C. parvum (n?=?44). Among them, C. parvum (27,610?±?71,911 oocysts/gram of feces) and the C. parvum-like genotype (38,679?±?82,811 oocysts/gram of feces) had higher oocyst shedding intensity than the C. ubiquitum-like genotype (2470?±?7017 oocysts/gram of feces) and the C. occultus (1012 oocysts/gram of feces). The C. parvum identified belonged to three subtypes in two rare subtype families, including IIpA9 (n?=?43), IIpA6 (n?=?6) and IIoA15G1 (n?=?9), while the C. parvum-like and C. ubiquitum-like genotypes generated very divergent gp60 sequences. CONCLUSIONS:Results of the present study suggest that bamboo rats on the study farms were infected with diverse Cryptosporidium species and divergent C. parvum subtypes, which probably had originated from their native habitats. As similar C. parvum subtypes have been recently detected in humans and farmed macaques, attentions should be paid to the potential role of these new farm animals in the transmission of zoonotic pathogens.

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.

Dataset Information

Divergent Copies of a Cryptosporidium parvum-Specific Subtelomeric Gene.

Publications

Divergent Copies of a <i>Cryptosporidium parvum</i>-Specific Subtelomeric Gene.

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