Pantothenic acid biosynthesis in the parasite Toxoplasma gondii: a target for chemotherapy

Antimicrob Agents Chemother. 2014 Jul 21. pii: AAC.02640-14. [Epub ahead of print

 

Mageed SN¹, Cunningham F¹, Hung AW², Silvestre HL³, Wen S², Blundell TL³, Abell C², McConkey GA⁴.

 

Toxoplasma gondii is a major food pathogen and neglected parasitic infection that causes eye disease, birth defects, and fetal abortion and plays a role as an opportunistic infection in AIDS. In this study, we investigated pantothenic acid (vitamin B5) biosynthesis in T. gondii. Genes encoding the full repertoire of enzymes for pantothenate synthesis and subsequent metabolism to Coenzyme A were identified and are expressed in T. gondii. A panel of inhibitors developed to target Mycobacterium tuberculosis pantothenate synthetase were tested and found to exhibit a range of inhibitions of growth of T. gondii. Two inhibitors exhibited lower effective concentrations than the current toxoplasmosis drug pyrimethamine. The inhibition was specific for the pantothenate pathway as the effect of the pantothenate synthetase inhibitors was abrogated by supplementation with pantothenate. Hence, T. gondii encodes and expresses the enzymes for pantothenate synthesis and this pathway is essential for parasite growth. These promising findings increase our understanding of growth and metabolism in this important parasite and highlight pantothenate synthetase as a new drug target.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PMID:

25049241

[PubMed - as supplied by publisher]