Publications

Commensal Oral Rothia mucilaginosa Produces Enterobactin, a Metal-Chelating Siderophore

Uranga CC, Arroyo P, Duggan BM, Gerwick WH, Edlund A

PMID: 32345739

Abstract

Next-generation sequencing studies of saliva and dental plaque from subjects in both healthy and diseased states have identified bacteria belonging to the genus as ubiquitous members of the oral microbiota. To gain a deeper understanding of molecular mechanisms underlying the chemical ecology of this unexplored group, we applied a genome mining approach that targets functionally important biosynthetic gene clusters (BGCs). All 45 genomes that were mined, representing , , and , harbored a catechol-siderophore-like BGC. To explore siderophore production further, we grew the previously characterized ATCC 25296 in liquid cultures, amended with glycerol, which led to the identification of the archetype siderophore enterobactin by using tandem liquid chromatography-mass spectrometry (LC-MS/MS), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) spectroscopy. Normally attributed to pathogenic gut bacteria, is the first commensal oral bacterium found to produce enterobactin. Cocultivation studies including or purified enterobactin revealed that enterobactin reduced growth of certain strains of cariogenic and pathogenic strains of Commensal oral bacteria were either unaffected, reduced in growth, or induced to grow adjacent to enterobactin-producing or the pure compound. Taken together with 's known capacity to ferment a variety of carbohydrates and amino acids, our findings of enterobactin production add an additional level of explanation to 's prevalence in the oral cavity. Enterobactin is the strongest Fe(III) binding siderophore known, and its role in oral health requires further investigation. The communication language of the human oral microbiota is vastly underexplored. However, a few studies have shown that specialized small molecules encoded by BGCs have critical roles such as in colonization resistance against pathogens and quorum sensing. Here, by using a genome mining approach in combination with compound screening of growth cultures, we identified that the commensal oral community member harbors a catecholate-siderophore BGC, which is responsible for the biosynthesis of enterobactin. The iron-scavenging role of enterobactin is known to have positive effects on the host's iron pool and negative effects on host immune function; however, its role in oral health remains unexplored. was previously identified as an abundant community member in cystic fibrosis, where bacterial iron cycling plays a major role in virulence development. With respect to iron's broad biological importance, iron-chelating enterobactin may explain 's colonization success in both health and disease.