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.

Highlights

  • Since early in the last century [1] the role of both vitamin A and vitamin D in combating infectious diseases has been investigated

  • We show that vitamin A, its metabolites Retinyl acetate, Retinoic acid and 13-cis Retinoic acid and vitamin D directly inhibit mycobacterial growth in culture

  • In this study we show that all M. avium subspecies paratuberculosis (MAP) and both M. tb complex strains are inhibited by Monensin (Table 1 and Figures 1 & 4 & Table 1 & Figures 3 & 6.) This corroborates our previous findings with Monensin [20,21,30]

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Summary

Introduction

Since early in the last century [1] the role of both vitamin A (see [2] for review) and vitamin D (see [3,4] for review) in combating infectious diseases has been investigated. The activities of vitamins A & D have been extensively reported in relation to the host immune response in mycobacterial diseases [4,8,11,12,13,14,15]. We posit that vitamins will have fundamental and necessary activity in both prokaryotes as well as eukaryotes. We hypothesized that vitamins A and D might directly inhibit prokaryotic growth in general and mycobacterial growth in particular. Any direct inhibitory action of vitamins would be in addition to (and possibly synergistic with) their effect on the immune response of a mycobacterial-infected host [5,6,7,8]. The 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, mycobacteria

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