Xylose utilization promotes Salmonella replication within macrophages and systemic infection in mice

The intracellular pathogen Salmonella can cause systemic diseases via its survival and replication in host macrophages. Xylose is the second most abundant sugar in nature and Salmonella can use xylose as its sole carbon source for growth. However, whether xylose utilization contributes to the pathogenicity and intracellular growth of Salmonella has not yet been determined. In this study, we observed that the xylose concentration in macrophages increased during Salmonella infection. Moreover, there was an increase in expression of Salmonella xylose catabolic genes (xylA and xylB) and the transcriptional regulatory gene of xylose metabolism (xylR) in macrophages, revealing the possibility of using host-accumulated xylose by Salmonella for intracellular growth. Mutation of either xylAB or xylR reduced Salmonella replication in macrophages and attenuated the colonization of mouse systemic loci (e.g. the liver and spleen), indicating that xylose utilization promotes Salmonella replication within macrophages and systemic infection in mice. Moreover, we found that xylose utilization by intracellular Salmonella was activated by the cAMP-CRP complex upon detection of low glucose levels in the infected macrophages. Collectively, these findings reveal that although the available glucose decreases during infection, Salmonella can use xylose, which accumulates in infected macrophages, as an alternative carbon source to promote intracellular replication and virulence.