Planta Med 2007; 73(6): 559-563
DOI: 10.1055/s-2007-981522
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

A Mycobacterium marinum Zone of Inhibition Assay as a Method for Screening Potential Antimycobacterial Compounds from Marine Extracts

Lucia P. Barker1 [*] , Benjamin A. Lien2 [*] , Olivier S. Brun1 , Damen D. Schaak3 , Kathleen A. McDonough3 , Leng Chee Chang2
  • 1University of Minnesota Medical School, Department of Anatomy Microbiology and Pathology, Duluth, MN, USA
  • 2Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, USA
  • 3Wadsworth Center, New York State Department of Health, Albany, NY, USA
Further Information

Publication History

Received: September 23, 2006 Revised: April 11, 2007

Accepted: April 15, 2007

Publication Date:
30 May 2007 (online)

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Abstract

A novel screening method for antimycobacterial agents using Mycobacterium marinum was developed. M. marinum was selected as a model organism because it has a close phylogenetic relationship to M. tuberculosis, a relatively rapid doubling time, similar drug susceptibilities to M. tuberculosis, and less stringent safety requirements. More than 1000 crude marine and plant extracts were screened against M. marinum in a Zone of Inhibition (ZOI) assay, and twenty-one target extracts were identified. The crude organic extract of the marine sponge, Haliclona sp.10, was chosen for further investigation as it yielded a ZOI of 20 mm at a concentration of 80 μg/disk. Following bioassay-guided fractionation, (-)-papuamine was isolated, and yielded a 15 mm ZOI at a concentration of 25 μg/disk. In standard assays using M. marinum, (-)-papuamine exhibited both an MIC and an MBC95 of 6.25 μg/mL. This is the first report of antimycobacterial activity for (-)-papuamine. In addition, when (-)-papuamine and other natural product extracts were tested for activity against both M. marinum and M. tuberculosis, activity was comparable between the two species. These data indicate that (-)-papuamine is a promising lead for the development of new antimycobacterial agents and that M. marinum is a useful surrogate for the screening of antimycobacterial compounds.