Ecology and evolution of secondary metabolite production in Bacilli

Carlos Neftaly Lozano Andrade*

*Corresponding author for this work

Research output: Book/ReportPh.D. thesis

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Soil microbes play diverse and often pivotal roles in ecosystem services, driving biogeochemical cycles, plant growth, and life above and below ground. These activities are performed by complex communities composed of several interacting species, rather than a single species. Thus, interactions are essential for all organisms, and it is believed that small molecules, acting as chemical mediators, are the driving force of microbial interplay. Classically, these small organic molecules, which encompass a high chemical diversity along with a multiplicity of functions, have been denominated as secondary metabolites and more recently ‘specialized’ metabolites given the dedicated role played in certain interactions. Secondary metabolites, unlike primary metabolites, are not directly associated with growth or proliferation but rather offer specific ecological or physiological advantages to their producer’s fitness in a particular environment. These natural products have been a pillar for modern medicine and biotechnological industries since many front-line drugs for treating infectious and cancer came from a microbial source. Despite the antibiotic and drug-discovery view, microbe-centered approaches have revealed a plethora of functions and roles of secondary metabolites, ranging from the so-evident inhibition of competitors to signaling molecules for coordinated behaviors. However, and besides the growing body of knowledge about secondary metabolites, our understanding of the ecological role of these molecules has just begun to be cracked.

In this thesis, I contributed to our comprehension of the natural role of secondary metabolites in a wild strain of Bacillus subtilis recently isolated from soil in Dyrehaven park, Denmark. Members of the B. subtilis species complex have been highlighted as prolific producers of secondary metabolites, being this trait one of the underlying mechanisms behind the beneficial activities exerted by strains of this genus.

Here, we specifically examined the influence of B. subtilis-produced cyclic lipopeptides during bacterial synthetic community (SynCom) assembly, and simultaneously, explored the impact of LPs on B. subtilis establishment success in both a soil-derived semi-synthetic microbial community and a simplified bacterial synthetic community propagated in artificial soil microcosms. Additionally, using analytical chemistry methods, we explored changes in the chemodiversity of both B. subtilis and the synthetic community when they were co-cultivated.

Using the semi-synthetic bacterial mock community approach, we found that cyclic lipopeptides had slight minor effect on the overall bacterial composition but influenced the abundance of the closely related genera Lysinibacillus and Viridibacillus. In addition, in vitro assays revealed that Lysinibacillus fusiformis M5 growth was affected by the presence of surfactin. Analogously, we employed a four-species synthetic bacterial community propagated in a soil-like matrix as reductionist approach to investigate the role of secondary metabolites in synthetic community assembly and B. subtilis ability to thrive such a well-controlled microenvironment. Under this approach, we found that surfactin production enables B. subtilis establishment within the SynCom. Surprisingly, while neither the wild type nor the lipopeptide non-producer strains had major impact on the SynCom composition over time, the B. subtilis and the SynCom metabolomes were both altered during co-cultivation.

Overall, the work presented in this thesis provides insight into the roles of secondary metabolites produced by B. subtilis, broadening our knowledge of these natural products in an ecological context. This insight, along with the methodological approaches developed in the thesis, can direct future studies aimed at unlocking the natural role of secondary metabolites.
Original languageEnglish
Place of PublicationKgs. Lyngby, Denmark
PublisherDTU Bioengineering
Number of pages171
Publication statusPublished - 2022


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