title: The thioamides methimazole and thiourea inhibit growth of M. avium Subspecies paratuberculosis in culture.
abstract: 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 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" (%-DeltacGI).
  
  
  RESULTS
  Methimazole was the most effective thioamide at inhibiting MAP growth. At 128microg/ml: MAP UCF-4; 65%-DeltacGI & MAP ATCC 19698; 90%-DeltacGI. Thiourea inhibited MAP "Ben" maximally; 70%-DeltacGI. 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, James J Peters VA Medical Center, Bronx, New York, United States of America. BGAxis@aol.com
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Greenstein
authors.forename: Liya
authors.initials: L
authors.lastname: Su
authors.forename: Sheldon T
authors.initials: ST
authors.lastname: Brown
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D008713:Methimazole / Q000494:pharmacology*; D009162:Mycobacterium avium / Q000187:drug effects* / Q000254:growth & development; D013890:Thiourea / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D008713:Methimazole; D013890:Thiourea