Discovery of Peptidic Siderophore Degradation by Screening Natural Product Profiles in Marine-Derived Bacterial Mono- and Cocultures.

Abstract

Coral reefs are hotspots of marine biodiversity, which results in the synthesis of a wide variety of compounds with unique molecular scaffolds, and bioactivities, rendering reefs an ecosystem of interest. The chemodiversity stems from the intricate relationships between inhabitants of the reef, as the chemistry produced partakes in intra- and interspecies communication, settlement, nutrient acquisition, and defense. However, the coral reefs are declining at an unprecedented rate due to climate change, pollution, and increased incidence of pathogenic diseases. Among pathogens, Vibrio spp. bacteria are key players resulting in high mortality. Thus, alternative strategies such as application of beneficial bacteria isolated from disease-resilient species are being explored to lower the burden of pathogenic species. Here, we apply coculturing of a coral-derived pathogenic species of Vibrio and beneficial bacteria and leverage recent advancements in untargeted metabolomics to discover engineerable beneficial traits. By chasing chemical change in coculture, we report Microbulbifer spp.-mediated degradation of amphibactins, produced by Vibrio spp. bacteria to sequester iron. Additional biochemical experiments revealed that the degradation occurs in the peptide backbone and requires the enzyme fraction of Microbulbifer. A reduction in iron affinity is expected due to the loss of one Fe(III) binding moiety. Therefore, we hypothesize that this degradation shapes community behaviors as it pertains to iron acquisition, a limiting nutrient in the marine environment, and survival. Furthermore, Vibrio sp. bacteria suppressed natural product synthesis by beneficial bacteria. Understanding biochemical mechanisms behind these interactions will enable engineering probiotic bacteria capable of lowering pathogenic burdens during heat waves and incidence of disease.