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Chania Clare: Bacterial microcompartment utilisation in the human commensal Escherichia coli Nissle 1917

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, 2, 3, 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 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, 8, 9]. EcN both directly and indirectly antagonises multiple enteropathogens through competition and in preventing systemic circulation [10, 11], as well as reducing the invasion capacity of Shiga-like toxin E. coli, Listeria monocytogenes, Salmonella enteritidis and Legionella pneumophila [12, 13, 14]. Additionally, EcN elicits anti-inflammatory and immune responses [15, 16], as well as contributing to the healthy function of the intestinal epithelial barrier [17].

Bacterial microcompartments (BMCs) encapsulate enzymatic pathways in self-assembling protein shells, and can be found across 23 bacterial phyla, expanding their metabolic potential [18, 19, 20]. The compartment can be beneficial in preventing the exposure of the cell to toxic intermediates, such as aldehydes by coupling its sink reactions to the recycling of an exclusive cofactor pool [21, 22, 23, 24], and in increasing the rate of reaction through the high concentration of enzymes [25]. Many examples of BMC-associated metabolic pathways are present in the human gut [26, 27], where they enable the catabolism of alternative substrates. They commonly confer competitive advantage to enteric pathogens when more typical substrates like glucose are restricted, enabling them to overcome colonisation resistance and rapidly populate the microbiota [28].

For example, in Salmonella enterica the capacity for EA catabolism enables the bacteria to sense different gut environments, and therefore enact optimal proliferation strategies, and to interact with the gut environment in order to outcompete the other resident bacteria [29]. In this way, not only does S. enterica utilise EA to increase the range of nutrients it can survive on and thus gain a competitive advantage, but is also uses this pathway to change the gut environment for its advantage and adapt to it itself. In anaerobic conditions, EA does not support significant growth through fermentation, however S. enterica induces the gut to produce tetrathionate as an alternative electron acceptor, enabling it to utilise EA even in anaerobic conditions [30, 31]. It is held that S. enterica uses this niche to rapidly proliferate and cause infection and dysbiosis in the human gut [32, 33]. However, this report looks to investigate whether the human gut commensal E. coli Nissle 1917 can also utilise this niche, and perhaps also the gut environment. This could reveal a point of competition that can be exploited for methods of bacterial community control.

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