Studies are proposed to evaluate the hypothesis that marine bacteria produce compounds that can inhibit the growth of mycobacteria. The control of mycobacteria is of significant concern throughout the world as pathogenic species, such as Mycobacterium tuberculosis, show increasing rates of resistance to the antibiotics currently available. A second hypothesis, based on preliminary observations in our laboratory as well as related work described in the literature, proposes that antibiotic production can be induced in marine bacteria. This hypothesis will be tested through the challenge of pure cultures of marine bacteria with a mycobacterium. If results of these experiments are consistent with previous observations, induction could represent a significant new tool in the search for novel antibiotic compounds. The mycobacteria to be used in the work art CSU San Marcos will include M. marinum, a marine/aquatic bacterium known to cause a disease commonly referred to as swimming pool granuloma. This mycobacterial species can be handled safely in our laboratory, and it can serve as an indicator species for anti- mycobacterial activity in general. In addition, 3 non-pathogenic mycobacterial strains encompassing a wide range of physiological characteristics found in mycobacteria will be purchased from the ATCC and used as indicator strains. Any extracts or pure compounds exhibiting inhibitory activity against any of the 4 indicator strains will be submitted to th4e TAACF for anti-tuberculosis screening. This proposal focuses on the isolation and culture of genera of marine bacteria previously shown to include producers of novel antibiotics, such as Chromacterium and Alteromonas. Bacterial isolates will be grown in pure culture and their metabolic products extracted. Each extract will then be tested for the presence of anti-mycobacterial compounds using an agar disk elution assay and chemical evaluation (NMR, TLC). Promising bacterial strains will be cultured on a large scale, and their extracts will be subjected to in-depth chemical and biological analyses. Chemical separation methods will include various chromatographic methods. Structure elucidation will be performing using a variety of modern spectroscopic techniques in conjunction with standard degradation, derivation and synthetic methods as needed. Biological assays will be conducted with each separation step. Overall, the research will target anti- mycobacterial compounds, with particular focus on the discovery of potential therapies for tuberculosis and infections caused by M. marinum.
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