Cryptosporidiosis, caused by the apicomplexan parasite Cryptosporidium parvum, is a moderate-to-severe diarrheal disease now recognized as one of the leading causes of morbidity and mortality in livestock globally, and in humans living in resource-limited parts of the world, particularly those with AIDS or malnourished individuals. This recognition has fueled efforts for the discovery of effective therapeutics. While recent progress in drug discovery has been encouraging, there are presently no acceptably effective parasite-specific drugs for the disease. The urgent need for new drug discovery or drug repurposing has also increased the need for refined animal models of clinical disease for therapeutic efficacy evaluation. Here, we describe an acute model of cryptosporidiosis using newborn calves to evaluate well-defined clinical and parasitological parameter outcomes, including the effect on diarrhea severity and duration, oocyst numbers produced, and multiple measures of clinical health. The model is highly reproducible and provides unequivocal direct measures of treatment efficacy on diarrhea severity and parasite replication.
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http://dx.doi.org/10.1007/978-1-4939-9748-0_15 | DOI Listing |
J Struct Biol
January 2025
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, PR China. Electronic address:
Cryptosporidium has gained much attention as a major cause of diarrhea worldwide. Here, we present the first structure of H-2K complexed with a decapeptide from Cryptosporidium parvum Gp40/15 protein (Gp40/15-VTF10). In contrast to all published structures, the aromatic residue P3-Phe of Gp40/15-VTF10 is anchored in pocket C rather than the canonical Y/F at P5 or P6 reported for octapeptides and nonapeptides.
View Article and Find Full Text PDFJ Biomol Struct Dyn
January 2025
Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju, Republic of Korea.
Cryptosporidiosis is an infection induced by the single-celled protozoan Cryptosporidium parasite. This parasite commonly infects the intestines of humans and animals, leading to gastrointestinal symptoms such as diarrhea, stomach cramps, nausea, and vomiting. Cryptopain protein, a type of cysteine protease found in the genome of plays an important role in cell invasion and its survival.
View Article and Find Full Text PDFNat Commun
December 2024
State Key Laboratory for Animal Disease Control and Prevention, Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
The anthroponotic Cryptosporidium hominis differs from the zoonotic C. parvum in its lack of infectivity to animals, but several divergent subtypes have recently been found in nonhuman primates and equines. Here, we sequence 17 animal C.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemistry, School of Science and Engineering, Saint Louis University, Saint Louis, Missouri 63103, United States.
Cryptosporidiosis is a diarrheal disease caused by the parasite resulting in over 100,000 deaths annually. Here, we present a structure-activity relationship study of the benzoic acid position (R) of pyrazolo[3,4-]pyrimidine lead SLU-2815 (), an inhibitor of parasite phosphodiesterase PDE1, resulting in the discovery of benzoxaborole SLU-10906 () as a benzoic acid bioisostere. Benzoxaborole is 10-fold more potent than against the parasite in a cell-based infection model (EC = 0.
View Article and Find Full Text PDFEnviron Res
December 2024
Department of Epidemiology and Biostatistics, Temple University Philadelphia, PA, USA; Water, Health and Applied Microbiology Lab, Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada. Electronic address:
Background: Campylobacter, nontyphoidal Salmonella, Cryptosporidium, and Giardia cause an estimated 1 million cases of domestically acquired waterborne diseases annually in the United States. Acute symptoms can include diarrhea and vomiting; however, these illnesses can result in longer term complications such as reactive arthritis, Guillan Barré syndrome and death, particularly in immunocompromised individuals. Precipitation and drought can plausibly increase the risk of enteric infections, but consensus in the literature is lacking.
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