title: Unanticipated Mycobacterium tuberculosis complex culture inhibition by immune modulators, immune suppressants, a growth enhancer, and vitamins A and D: clinical implications.
abstract: BACKGROUND
  The development of novel antibiotics to treat multidrug-resistant (MDR) tuberculosis is time-consuming and expensive. Multiple immune modulators, immune suppressants, anti-inflammatories, and growth enhancers, and vitamins A and D, inhibit Mycobacterium avium subspecies paratuberculosis (MAP) in culture. We studied the culture inhibition of Mycobacterium tuberculosis complex by these agents.
  
  
  METHODS
  Biosafety level two M. tuberculosis complex (ATCC 19015 and ATCC 25177) was studied in radiometric Bactec or MGIT culture. Agents evaluated included clofazimine, methotrexate, 6-mercaptopurine, cyclosporine A, rapamycin, tacrolimus, monensin, and vitamins A and D.
  
  
  RESULTS
  All the agents mentioned above caused dose-dependent inhibition of the M. tuberculosis complex. There was no inhibition by the anti-inflammatory 5-aminosalicylic acid, which causes bacteriostatic inhibition of MAP.
  
  
  CONCLUSIONS
  We conclude that, at a minimum, studies with virulent M. tuberculosis are indicated with the agents mentioned above, as well as with the thioamide 5-propothiouricil, which has previously been shown to inhibit the M. tuberculosis complex in culture. Our data additionally emphasize the importance of vitamins A and D in treating mycobacterial diseases.
authors.affiliation: Department of Surgery, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA; Laboratory of Molecular Surgical Research, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA. Electronic address: BGAxis@aol.com.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Greenstein
authors.affiliation: Laboratory of Molecular Surgical Research, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
authors.forename: Liya
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Pathology, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
authors.forename: Azra
authors.initials: A
authors.lastname: Shahidi
authors.affiliation: Laboratory of Molecular Surgical Research, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Brown
authors.affiliation: Laboratory of Molecular Surgical Research, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
authors.forename: Anya
authors.initials: A
authors.lastname: Clifford
authors.affiliation: Infectious Disease Section, James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA; Department of Medicine, Icahn School of Medicine at Mt. Sinai, New York, USA.
authors.forename: Sheldon T
authors.initials: ST
authors.lastname: Brown
mesh_terms: D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008985:Monensin / Q000494:pharmacology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000187:drug effects; D009163:Mycobacterium bovis / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014801:Vitamin A / Q000494:pharmacology*; D014807:Vitamin D / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D000904:Antibiotics, Antitubercular; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D014815:Vitamins; D014801:Vitamin A; D014807:Vitamin D; D008985:Monensin
keywords: Clofazimine; Mycobacterium avium subspecies paratuberculosis; Thioguanine; Tuberculosis; Vitamin A; Vitamin D