Cottam, C. | bioRxiv Science

bioRxiv2023

Metabolism of ʟ -arabinose converges with virulence regulation to promote enteric pathogen fitness

Virulence and metabolism are often interlinked to control the expression of essential colonisation factors in response to host-associated signals. Here, we identified a novel transporter of the dietary monosaccharide -arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagic Escherichia coli (EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Accordingly, we discovered that -arabinose induces expression of the EHEC type 3 secretion system, enhancing its ability to attach to host cells, and that the underlying mechanism is dependent on products of its catabolism rather than the sensing of -arabinose as a signal. Finally, using the murine pathogen Citrobacter rodentium, we show that -arabinose metabolism provides a fitness benefit during enteric infection via virulence factor regulation, as opposed to supporting pathogen growth. This study describes an intrinsic mechanism of integrating central sugar metabolism with virulence regulation and highlights the unexpected impact that nutrient utilisation can have in enteric pathogens.

microbiology↗

bioRxiv2022

The Type 9 Secretion System enables sharing of fungal mannan by human gut Bacteroides

Degradation of complex carbohydrates in the gut is a key trait of Bacteroides species. Some glycans are metabolised selfishly releasing few or no oligosaccharide breakdown products from complex polysaccharides, whereas others release oligosaccharides and cross feed other microbes. The outer cell wall of many fungi commonly found in the gut consists of highly -mannosylated proteins which have been shown to be metabolised in a selfish manner by Bacteroides thetaiotaomicron. We show that the species Bacteroides salyersiae releases branched manno-oligosaccharides during growth on mannan and that these act as a nutrient source for Bacteroides spp. that are unable to degrade polymeric mannan. Molecular characterisation of the locus responsible for mannan degradation reveals that it contains multiple glycoside hydrolases and glycan binding proteins targeted to the Type 9 Secretion System, a Bacteroidetes specific secretion system that allows the secretion of large folded proteins across the outer membrane. More commonly found in oral and environmental Bacteroidetes, here the T9SS enables B. salyersiae to locate large, multimodular enzymes and glycan binding proteins outside the cell to target a complex, branched polysaccharide. This points to a previously unknown role of the T9SS in glycan metabolism in gut Bacteroides.

microbiology↗