The potential of microbial secondary metabolites in marine systems and their influence on microbial diversity

Microorganisms can produce many different and highly specialized secondary metabolites. These compounds have predominantly been known for their antibiotic properties, due to their history of being used to treat infectious human pathogens. Consequently, antimicrobial secondary metabolites have been well studied under laboratory conditions, but far less is known about their actual functions and role(s) as well as their producers in the natural environment. Antibiotic secondary metabolites have generally been described as mediators of hostile competition between microbes and thus, microbial secondary metabolites are considered to play important roles in microbial interactions. Nonetheless, we still do not understand if and how these compounds affect the assembly and development of microbial communities in nature, where their ecological role might expand much beyond microbial antagonism.
In the work of this thesis, we focused on the marine environment and marine microorganisms, since they, compared to the terrestrial environment, have been far less explored with respect to the secondary metabolite potential. The purpose of this PhD project was to explore the genetic secondary metabolite diversity of marine microbial communities and unravel if and how microbial secondary metabolism can shape microbial communities.
In the first study, we adapted an amplicon-based sequencing approach as a proxy for the genetic secondary metabolite potential in natural environmental samples. Targeted sequencing of conserved AD and KS domains within BGCs encoding NRPSs and PKSs, respectively, revealed that seawater, and particularly sandy sediments hold a high genetic potential for secondary metabolite production that is also is distinct from the potential found in soil microbiomes.
In the second study, we addressed the implications of microbial secondary metabolite production on the assembly dynamics of marine microbial communities. We focused on the marine biofilm forming and TDA-producing P. inhibens. A semi-natural model system was constructed to study the assembly dynamics of a seawater biofilm community, that was exposed to either the P. inhibens WT with the capability to produce the antibiotic TDA or a mutant incapable of TDA production. We showed that 1.9% of the microbial composition variance could be attributed to the presence of the wild type P. inhibens, and that especially the relative abundance of Bacteriodetes peaked during the biofilm succession in the model system with the WT P. inhibens relative to the mutant and control system.
In the third study, we studied the temporal patterns of a natural biofilm succession in seawater conducted in situ. Findings from multi-omics (16S- 18S- and AD amplicon sequencing, genome resolved metagenomics and metabolomics) to track the taxon, BGC and metabolome dynamics of surface associated communities during marine biofilm succession suggested that the early marine biofilm formation favoured bacterial community members with higher BGC potential. This early phase of the biofilm succession, where furthermore associated with more metabolic features, while the later phases was dominated by multicellular eukaryotes and a reduction in microbial BGC potential.
In conclusion, this work has contributed to the understanding of microbial community assembly, highlighting the importance of temporal studies to display dynamic changes of the genetic microbial secondary metabolite potential and thus the possible production of secondary metabolites and their impact on microbial community succession. Finally, hypotheses generated from these studies will provide inspiration to efforts aiming toward improving culture-based approaches both for mechanistic understanding of secondary metabolites, but also for targeted search of microbiomes that are promising troves of novel chemistry for antibiotic drug discovery in future studies.