Chemotype to Phenotype Studies of Bacterial-Fungal Interactions

Bacteria and fungi frequently co-occur within complex multispecies microbiomes. While many microbiome studies have linked bacterial presence, and in some cases their metabolites, to health and disease states, fungi are often overlooked and understudied in these systems. Correlations between bacterial and fungal abundances based on metagenomics indicate that bacterial-fungal interactions are central to many microbiomes, and the mechanisms that drive these interactions impact microbiome formation and persistence. In most cases, microbial interactions involve excretion of and responses to secondary metabolites and studies that examine bacterial-fungal interactions often highlight the importance of these secondary metabolites. However, most of these studies are done on a case-by-case basis and are not necessarily translatable across different biological systems. With this dissertation I used a simplified model system for studying complex microbiomes and examine secondary metabolites that drive bacterial-fungal interactions within that model system. Various forms of mass spectrometry and analytical chemistry were employed to perform metabolomics experiments which were combined with genomic and transcriptomic information provided by our collaborators. This multi-omics approach provided a comprehensive overview of the bacterial-fungal interactions studied to shed light on the biological mechanisms that affect growth and stability within this model system. Patterns of conserved mechanisms that emerge may be translatable to higher order microbiomes.