exploits host- and bacterial-derived β-alanine for replication inside host macrophages.

is a major foodborne pathogen that can effectively replicate inside host macrophages to establish life-threatening systemic infections. must utilize diverse nutrients for growth in nutrient-poor macrophages, but which nutrients are required for intracellular growth is largely unknown. Here, we found that either acquisition from the host or de novo synthesis of a nonprotein amino acid, β-alanine, is critical for replication inside macrophages. The concentration of β-alanine is decreased in -infected macrophages, while the addition of exogenous β-alanine enhances replication in macrophages, suggesting that can uptake host-derived β-alanine for intracellular growth. Moreover, the expression of the rate-limiting gene required for β-alanine synthesis in is upregulated when enters macrophages. Mutation of impaired replication in macrophages and colonization in the mouse liver and spleen, indicating that de novo synthesis of β-alanine is essential for intracellular growth and systemic infection. Additionally, we revealed that β-alanine influences intracellular replication and in vivo virulence partially by increasing expression of the zinc transporter genes , which in turn facilitates the uptake of the essential micronutrient zinc by . Taken together, these findings highlight the important role of β-alanine in the intracellular replication and virulence of , and is a promising target for controlling systemic infection.