Xylose utilization promotes <i>Salmonella</i> replication within macrophages and systemic infection in mice

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