Continuous production of an antimicrobial metabolite with the terrestrial cyanobacterium Chroococcidiopsis cubana

Abstract

The terrestrial cyanobacterium Chroococcidiopsis cubana was identified as a producer of an antimicrobial substance inhibiting growth of the Gram-positive bacterium Micrococcus luteus and the yeast Candida auris. It was found that the production is initiated by nitrogen limitation, usually occurring during late exponential growth phase of the cyanobacterium. This effect was used for implementation of a continuous production set-up, which led to a significantly increased formation of the antimicrobial metabolite. The produced bioactive culture supernatant was purified by reverse phase chromatography; the most potent fraction caused a growth inhibition of over 90 % for both indicator organisms. The metabolite remained active until a temperature of approx. 45 °C; at increasing temperatures, the inhibiting effect decreased significantly. By identification of the trigger initiating the compound synthesis, a first scale-up could be implemented, leading to a reliable production of the antimicrobial metabolite. As Candida auris is an emerging pathogen causing serious infections, this work can be the first step to the development of a potent antifungal drug.