Evaluation of anti-tuberculosis secondary metabolites from Deep Lake Michigan sediment strain Micromonospora tulbaghiae

Our research program focuses on discovering novel therapies to treat TB. Following similar principles that led researchers to turn to the ocean for drug-leads, we have expanded this exploration to freshwater habitats, to which extraordinarily little is known about the endemic microbial and chemical diversity. Upon screening fractions of secondary metabolites from freshwater actinomycetes against M. tuberculosis (strain H₃₇Rv), we discovered that a strain (B006) collected from deep Lake Michigan sediment produced several submicromolar anti-TB secondary metabolites. We cultivated B006 in 30 L of freshwater media, extracted the extracellular metabolites, and after several chromatographic steps we isolated six metabolites that exhibited low micromolar potency growth inhibition against a panel of drug-resistant mycobacterial strains. In addition, one compound and a fraction containing a mixture of derivatives exhibited antibiotic activity toward a panel of the Gram-positive pathogens, though with markedly less potency when compared with activity against mycobacterial strains. The molecules are currently being further profiled with respect to selectivity, cidality, protein-mediated MIC shift and activity against a panel of M. tuberculosis global clade representives.