The marine environment has emerged as a key source of natural product drug leads. Screening unique organisms from rare or extreme ecosystems is a proven approach to discover novel compounds with important biological effects. Deep-sea hydrothermal vents are among the most dynamic and extreme environments on Earth. Because unique microbial organisms inhabit the regions near these vents, there is a strong likelihood that new bioactive small-molecule natural products will be discovered, given that it is well established that chemical diversity is directly proportional to biological diversity. A remotely operated vehicle (ROV) exploration of Kolumbo submarine volcano (500 m depth) in the Aegean Sea revealed a very active high-temperature hydrothermal vent field, emitting colourless gas plumes with temperatures recorded as high as 220°C. (Fig. 1) The goal of this study was to screen cultured vent mesophilic bacteria (Fig. 2) for antimicrobial activity.