The Thioamides Methimazole And Thiourea Inhibit Growth Of M. Avium Subspecies Paratuberculosis In Culture

Background: Thyrotoxicosis is conceptualized as an "autoimmune'' disease with no accepted infectious etiology. There are increasingly compelling data that another "autoimmune'' affliction, Crohn disease, may be caused by Mycobacterium avium subspecies paratuberculosis (MAP). Like M. tb, MAP is systemic. We hypothesized that some cases of thyrotoxicosis may be initiated by a MAP infection. Because other thioamides treat tuberculosis, leprosy and M. avium complex, we hypothesized that a mode of action of some thioamide anti-thyrotoxicosis medications may include MAP growth inhibition.Methods: The effect of the thioamides, thiourea, methimazole and 6-propo-2-thiouracil (6-PTU) were studied in radiometric Bactec (R) culture, on ten strains of three mycobacterial species (six of MAP, two of M. avium and two of M. tb. complex). Data are presented as "cumulative growth index,'' (cGI) or "percent decrease in cumulative GI'' (%-Delta cGI).Principal Findings: Methimazole was the most effective thioamide at inhibiting MAP growth. At 128 mu g/ml: MAP UCF-4; 65%-Delta cGI & MAP ATCC 19698; 90%-Delta cGI. Thiourea inhibited MAP "Ben'' maximally; 70%-Delta cGI. Neither methimazole nor thiourea inhibited M. avium or M. tb. at the doses tested. 6-PTU has no inhibition on any strain studied, although a structurally analogous control, 5-PTU, was the most inhibitory thioamide tested.Significance: We show inhibition of MAP growth by the thioamides, thiourea and methimazole in culture. These data are compatible with the hypothesis that these thioamides may have anti-prokaryotic in addition to their well-established eukaryotic actions in thyrotoxic individuals.