The Impact of Vitamin D3 on Mycobacterium Tuberculosis

Background: The direct impact of vitamin D (D) on Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, was studied previously. Two systematic and controversial studies showed that D2 inhibit the growth of M.tb on solid medium or D3 reduces the C14 emission by 60% in broth. This study investigated the direct impact of D3 on M.tb activity and gene expression. The mce4, cholesterol importer, found to be essential for M.tb growing on cholesterol and persistence though was not tested with another lipid. Thus, his study hypothesis that the expression of mce4 may be affected in the presence of D3. In addition, M.tb exposed to D3 may affect genes involved in cholesterol catabolism and dosR, persistence associator. Method: This study developed the 3H uracil incorporation in a destructive sampling method of detection to indicate the activity of M.tb in detergent free condition. Finding: The CPM of M.tb in D3 was less than the control on day two with p <0.0001, while it was higher than the control with p 0.001 on day fourteen. The CPM of M.tb in pH5 with D3 was higher than in glycerol with p 0.01. The exposure to D3 upregulates mce4A and dosR higher than glycerol by 2-folds and 12-folds respectively. M.tb exposed to cholesterol prior D3 upregulates mce4D by 3-folds, cyp124 by 3-folds, cyp125 by 4-folds, and dosR by 27-folds. Conclusion: Unlike glycerol, D3 reduces the activity of M.tb during lag phase and enhances it during stationary phase. In addition, D3 upregulates mce4A and dosR solely higher than in glycerol; however, the prior exposure to cholesterol upregulates mce4D, cyp124, cyp125, and dosR when exposed to D3 higher than in solel cholesterol. This finding shows that cholesterol has a modulatory effect on M.tb that enhances the metabolism of D3.