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Chania Clare: Bacterial microcompartment utilization in the human commensal Escherichia coli Nissle 1917
Bacterial microcompartments (BMCs) are self-assembled protein structures often utilized by bacteria as a modular metabolic unit, enabling the catalysis and utilization of less common carbon and nitrogen sources within a self-contained compartment. The ethanolamine (EA) utilization (eut) BMC has been widely demonstrated in enteropathogens, such as Salmonella enterica, and current research is exploring its activity in the commensal species that populate the human gut.
Escherichia coli Nissle 1917 (EcN) is a strong colonizer and probiotic in gut microbial communities and has been used extensively for microbiome engineering. In this study, the utilization of ethanolamine as a sole carbon source and the formation of the eut BMC in EcN were demonstrated through growth assays and visualization with transmission electron microscopy. Subsequently, flux balance analysis was used to further investigate the metabolic activity of this pathway. It was found that not only is the utilization of the eut BMC for the degradation of EA as a carbon source in EcN comparable with that of Salmonella enterica but also that ammonium is released into solution as a byproduct in EcN but not in S. enterica. Control of EA-dependent growth was demonstrated using different concentrations of the operon inducer, vitamin B12. We show that vitamin B12-dependent EA utilization as the sole carbon source enables growth in EcN, and demonstrate the concurrent formation of the BMC shell and inducible control of the eut operon.
The human gut comprises a complex interplay of microorganisms, metabolites, and enzymes, where dysbiosis (disruption in the healthy state of the microbiota) is linked to a multitude of health problems (1–4). The ecology of this community is complex and can be difficult to restore when perturbed. For example, under specific circumstances, a commensal strain of bacteria may become an opportunistic pathogen, which requires the administration of antibiotics to remove (5). As many antibiotics are non-specific, they can have widespread detrimental effects throughout the gut microbial community, as well as contributing to the increasing prevalence of antimicrobial resistance (6). Therefore, to understand how to control and treat dysbiosis in a more nuanced predictable manner, it is important to understand not only the colonisation mechanisms of these bacteria but also their interactions within the gut environment.
Escherichia coli Nissle 1917 (EcN) plays an important role in preventing pathogen-driven dysbiosis, where EcN is commonly used as a probiotic and target of bioengineering to promote and maintain a diverse and stable gut microbial population (7–9) and has been utilized as a chassis for therapeutics currently in phase 1 trials (10). EcN both directly and indirectly antagonizes multiple enteropathogens through competition and in preventing systemic circulation (11, 12), as well as reducing the invasion capacity of Shiga-like toxin E. coli, Listeria monocytogenes, Salmonella enteritidis, and Legionella pneumophila (13–15). Additionally, EcN elicits anti-inflammatory and immune responses (16, 17), as well as contributing to the healthy function of the intestinal epithelial barrier (18).