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

Abstract

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 ʟ-arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagicEscherichia coli(EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Accordingly, we discovered that ʟ-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 ʟ-arabinose as a signal. Finally, using the murine pathogenCitrobacter rodentium,we show that ʟ-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.