Identification of novel antimicrobial drugs from microbes in extreme environments

The cryosphere represents a relatively unexploited ecosystem in terms of antimicrobial drug discovery. Microbes residing in these environments tend with extreme environmental stresses, such as low temperature, variable salinity and UV fluctuations. Therefore, it is posited that microbes here produce novel compounds in response to these environmental stresses. These novel compounds may have antimicrobial activity. Initially, a culture collection was established using environmental samples from Svalbard (Chapter 3), Sweden and the Alps (Chapter 4). These isolates were compared against previously published cultivation collections from the cryosphere and success of cultivation strategies to capture inherent heterotrophic bacterial diversity is discussed (Chapter 5). These 291 isolates were then screened for potential antimicrobial activity against strains of clinically relevant bacteria (Chapter 6). A subset of these were then selected for Whole Genome Sequencing, to enable genome mining of phenotypically interesting strains (Chapter 7). Following identification of a likely novel species within the Cryobacterium genus, Cryobacterium isolates were compared against publicly available Cryobacterium genomes (Chapter 8) and the genus was assessed on inherent Biosynthetic Gene Cluster (BGC) profiles. A pangenome was also generated using these sequences and the genus diversity is discussed. This thesis identified candidate strains with cross-species antimicrobial activity, but also uncovered wide-spread growth-promotion effects of cryosphere bacteria metabolites, providing information of microbial ecology of the cryosphere.