The shikimate pathway enzyme that generates chorismate is not required for the development of Plasmodium berghei in the mammalian host nor the mosquito vector |
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Authors: | Hadi Hasan Choudhary Pratik Narain Srivastava Subhash Singh Kota Arun Kumar Satish Mishra |
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Institution: | 1. Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow 226031, India;2. CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India;3. Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India |
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Abstract: | In Plasmodium, the shikimate pathway is a potential target for malaria chemotherapy owing to its absence in the mammalian host. Chorismate, the end product of this pathway, serves as a precursor for aromatic amino acids, Para-aminobenzoic acid and ubiquinone, and is synthesised by Chorismate synthase (CS). Therefore, it follows that the Cs locus may be refractory to genetic manipulation. By utilising a conditional mutagenesis system of yeast Flp/FRT, we demonstrate an unexpectedly dispensable role of CS in Plasmodium. Our studies reiterate the need to establish an obligate reliance on Plasmodium metabolic enzymes through genetic approaches before their selection as drug targets. |
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Keywords: | Malaria Sporozoites Shikimate pathway Chorismate synthase |
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