Background: Cryptosporidium spp. are enteric protozoan parasites that infect a wide range of animals as well as humans. The studies on Cryptosporidium infections of animals in Turkey are mostly rely on microscopic observation. Few data are available regarding the distribution of Cryptosporidium genotypes and subtypes infection. The aim of this study is to analyse the zoonotic potential of Cryptosporidium oocysts shed from young ruminant livestock. Methods: A total of 415 diarrheic fecal specimens from 333 calves, 67 lambs, and 15 goat kids were examined for the presence of Cryptosporidium oocysts by microscopy. Microscopic positive specimens were then analyzed for Cryptosporidium genotypes and subtypes detection by use of nested PCR of the small subunit ribosomal RNA (SSU rRNA) gene and the highly polymorphic 60 kDa glycoprotein (gp60) gene followed by sequence analyses. Results: The results of this study revealed that 25.6% (106 of 415) of the specimens were positive for Cryptosporidium spp. infection by microscopic examination and molecular analysis. We identified 27.4% (91/333), 19.4% (13/67), and 13.4% (2/15) of positivity in calves, lambs and goat kids, respectively. Genotyping of the SSU rRNA indicated that almost all positive specimens were of C. parvum , except for one calf which was of C. bovis. Sequence analysis of the gp60 gene revealed the most common zoonotic subtypes (IIa and IId) of C. parvum. We detected 11 subtypes (IIaA11G2R1,

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Inosine 5′-monophosphate dehydrogenase (IMPDH) is an essential enzyme for the production of guanine nucleotides. Disruption of IMPDH activity has been explored as a therapeutic strategy for numerous purposes, such as for anticancer, immunosuppression, antiviral, and antimicrobial therapy. In the present study, we established a luciferase-based high-throughput screening system to identify IMPDH inhibitors from our chemical library of known bioactive small molecules. The screening of 1400 compounds resulted in the discovery of three irreversible inhibitors: disulfiram, bronopol, and ebselen. Each compound has a distinct chemical moiety that differs from other reported IMPDH inhibitors. Further evaluation revealed that these compounds are potent inhibitors of IMPDHs with kon values of 0.7 × 104 to 9.3 × 104 M−1·s−1. Both disulfiram and bronopol exerted similar degree of inhibition to protozoan and mammalian IMPDHs. Ebselen showed an intriguing difference in mode of inhibition for different IMPDHs, with reversible and irreversible inhibition to each Cryptosporidium parvum IMPDH and human IMPDH type II, respectively. In the preliminary efficacy experiment against cryptosporidiosis in severe combined immunodeficiency (SCID) mouse, a decrease in the number of oocyst shed was observed upon the oral administration of disulfiram and bronopol, providing an early clinical proof-of-concept for further utilization of these compounds as IMPDH inhibitors.