Vitamins A & D Inhibit the Growth of Mycobacteria in Radiometric Culture

Abstract

BackgroundThe role of vitamins in the combat of disease is usually conceptualized as acting by modulating the immune response of an infected, eukaryotic host. We hypothesized that some vitamins may directly influence the growth of prokaryotes, particularly mycobacteria.MethodsThe effect of four fat-soluble vitamins was studied in radiometric Bactec® culture. The vitamins were A (including a precursor and three metabolites,) D, E and K. We evaluated eight strains of three mycobacterial species (four of M. avium subspecies paratuberculosis (MAP), two of M. avium and two of M. tb. complex).Principal FindingsVitamins A and D cause dose-dependent inhibition of all three mycobacterial species studied. Vitamin A is consistently more inhibitory than vitamin D. The vitamin A precursor, β-carotene, is not inhibitory, whereas three vitamin A metabolites cause inhibition. Vitamin K has no effect. Vitamin E causes negligible inhibition in a single strain.SignificanceWe show that vitamin A, its metabolites Retinyl acetate, Retinoic acid and 13-cis Retinoic acid and vitamin D directly inhibit mycobacterial growth in culture. These data are compatible with the hypothesis that complementing the immune response of multicellular organisms, vitamins A and D may have heretofore unproven, unrecognized, independent and probable synergistic, direct antimycobacterial inhibitory activity.

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

“…124 Further trials are required to accurately define the value of vitD3 as TB HDT. Vitamin A (vitA) possesses host immunomodulatory potential and in vitro anti-mycobacterial capabilities, 125 deficiency strongly predicts the risk of incident TB amongst TB household contacts (HHC) and supplementation (with zinc) improves TB treatment outcomes. 126 The vitA derivative, all-trans-retinoic acid (ATRA), decreased Mtb burden by reducing cellular cholesterol and inducing phagosomal acidification.…”

Potent Antimycobacterial Activity of the Pyridoxal Isonicotinoyl Hydrazone Analog 2-Pyridylcarboxaldehyde Isonicotinoyl Hydrazone: A Lipophilic Transport Vehicle for Isonicotinic Acid Hydrazide

“…Strategies to improve tuberculosis drug therapy include the modification of existing drugs and the development of novel antibiotics, and a number of promising candidates have been described (Wong et al, 2013). There has also been interest in the implementation of nutrient supplementation to control tuberculosis, either as a stand-alone therapy or as an adjunct treatment for use with current drug regimens (Sinclair et al, 2011;Greenstein et al, 2012).…”

Sharpening nature's tools for efficient tuberculosis control: A review of the potential role and development of host-directed therapies and strategies for targeted respiratory delivery

“…Successful reduction in bacterial viability up to 7 days was evident in both instances, with treatment post-infection exhibiting the greatest effect [36]. Other studies have shown anti-bacterial effects on mycobacteria in culture, indicating both pathogen-targeted and host-targeted effects [40,41]. Anti-bacterial properties of atRA in vivo have been demonstrated in Mtb infected Wister-Lewis rats alongside promising histopathology results [42].…”

“…Once metabolised from 7-dehydrocholesterol to 25-dihydroxyvitamin D3 and subsequently to 1,25-dihydroxyvitamin D3 (1,25D), the fat soluble vitamin acts on the vitamin D receptor, heterodimerizing with the same nuclear retinoid X receptor family as atRA, which is often studied in parallel [39]. Anti-mycobacterial action has been documented since the 1980s, with slowed intracellular Mtb growth demonstrated in human macrophages treated with 1,25D [65,66] and in mycobacterial culture using Mycobacteria Growth Indicator Tube (MGIT) and BACTEC™ culture systems [40,41].…”