Para -Aminosalicylic Acid Acts as an Alternative Substrate of Folate Metabolism in Mycobacterium tuberculosis

Author:

Chakraborty Sumit12,Gruber Todd3,Barry Clifton E.3,Boshoff Helena I.3,Rhee Kyu Y.12

Affiliation:

1. Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA.

2. Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.

3. Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute for Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.

Abstract

Poisoned Pathways Fifty years ago, para -aminosalicyclic acid (PAS) was developed as an antituberculosis drug. Since then, it has been assumed that PAS acts to competitively inhibit para -aminobenzoate (PABA) from entering the folate pathway at the enzyme dihydropteroate synthase (DHPS). Strangely, the well-known inhibitors of DHPS—the sulfonamide drugs—are useless in tuberculosis treatment, although they are effective against other microbial pathogens. Chakraborty et al. (p. 88 , published online 1 November) addressed this conundrum by comparing the effect of several sulfonamides, as well as PAS and PABA, on the folate pathway of live Mycobacterium tuberculosis. It seems the bacterium is better at inactivating sulfonamides than PAS and that PAS does not really compete with PABA. Instead, PAS cascades through the folate pathway generating a series of poisonous intermediates.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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