Revitalizing antifolates through understanding mechanisms that govern susceptibility and resistance

Shannon Lynn Kordus, Anthony David Baughn

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

In prokaryotes and eukaryotes, folate (vitamin B9) is an essential metabolic cofactor required for all actively growing cells. Specifically, folate serves as a one-carbon carrier in the synthesis of amino acids (such as methionine, serine, and glycine), N-formylmethionyl-tRNA, coenzyme A, purines and thymidine. Many microbes are unable to acquire folates from their environment and rely on de novo folate biosynthesis. In contrast, mammals lack the de novo folate biosynthesis pathway and must obtain folate from commensal microbiota or the environment using proton-coupled folate transporters. The essentiality and dichotomy between mammalian and bacterial folate biosynthesis and utilization pathways make it an ideal drug target for the development of antimicrobial agents and cancer chemotherapeutics. In this minireview, we discuss general aspects of folate biosynthesis and the underlying mechanisms that govern susceptibility and resistance of organisms to antifolate drugs.

Original languageEnglish (US)
Pages (from-to)880-895
Number of pages16
JournalMedChemComm
Volume10
Issue number6
DOIs
StatePublished - Jun 1 2019

Bibliographical note

Funding Information:
This work was supported by startup funds from the University of Minnesota, an Academic Health Center Faculty Research Development Program award and NIH grant AI123146 to ADB, and a University of Minnesota Doctoral Dissertation Fellowship awarded to SLK.

Publisher Copyright:
© 2019 The Royal Society of Chemistry.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

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