Culturing the unculturable: Expanding the diversity of marine microorganisms for drug discovery

Although explorations of bacteria and fungi have been an exceptional source for new drug development, surprisingly only a small percentage of the genetic diversity in these groups has been accessed. In the bacteria, for example, less than an estimated 5% of the known taxa have been successfully cultivated and explored chemically. Resistance to cultivation has been convincingly demonstrated by the “Great Plate Anomaly,” in which less than 5% of the cells present by direct microscopic observation can be shown to grow. This has been interpreted to suggest that the vast majority of environmental bacteria are resistant to cultivation. In the marine environment, the same situation exists; bacteria isolated from seawater or sediments are largely unable to be cultured using standard conditions. But are they really unable to be cultured? By systematically varying the culture conditions we have found that previously undiscovered bacterial strains can be readily brought into culture. These methods and new approaches now allow chemical studies of rare and previously unknown strains to become part of the drug discovery process. Several examples of new molecules isolated from these strains will be presented.