Cryptosporidiosis: Challenges for Chemotherapy to AIDS Subpopulation

Kalpana ¹ , R.K. Srivastava² , R. Nath³ , N. Singh⁴

Section:Review Paper, Product Type: Isroset-Journal
Vol.5 , Issue.2 , pp.26-32, Apr-2017

Online published on Apr 30, 2017

Copyright © Kalpana, R.K. Srivastava, R. Nath, N. Singh . This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
 

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Abstract :
Cryptosporidium parasites, especially C.parvum and C.hominis are obligate intracellular apicomplexans protozoan parasite that infect epithelial cells of the small intestine posing life threatening Cryptosporidiosis disease to immunocompromised person and young malnourished children. It is also well known to be a troublesome waterborne pathogen. Pathogen transmission is naturally via contaminated drinking or recreational water supplies by the environmentally resistant and chlorine resistant oocysts. Cryptosporidium is classified in category B of bioweapons agents. However nitazoxanide, a nitrothiazole benzamide was approved by FDA Department for treatment of cryptosporidiosis in immunocompetent individuals and Paramomycin is used to treat C.parvum infections in animals. Cryptosporidium infections starts by ingestion of oocysts with contaminated water or food. Oocysts undergo excystation in gastrointestinal tract where four naked sporozoites are formed which then infect epithelial cell and initiate asexual development. IMPDH an NAD+ enzyme remains a promising drug target for anti-parasitic drugs. Cryptosporidium obtains guanine nucleotides via a streamlined pathway that requires IMPDH. Curiously, the gene encoding CpIMPDH seems to have been obtained from a bacteria through lateral gene transfer so that the parasite enzyme is very different from host ortholog. IMPDH is a homotetramer showing square planner symmetry. Inhibition of IMPDH is already used to treat viral infection and could be used to treat parasitic infection as well. IMPDH has been isolated from different sources and 26 crystal structure are deposited in PDB including mammals to apicomplexans and bacteria. There are several FDA approved inhibitors that target IMPDH.

Key-Words / Index Term :
Cryptosporidium Parvum, Cryptosporidiosis, GMP, IMP, Immunocompromised, Immunocompetent, IMPDH, PVM , XMP

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