
沙門氏菌需要利用宿主來源或自身合成的β-丙胺酸來促進細胞內複製和增強毒力，其機制部分是通過β-丙胺酸促進鋅轉運蛋白基因的表達來實現的。


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

### Competing Interest Statement

The authors have declared no competing interest.

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

沙門氏菌利用宿主和自身來源的β-丙胺酸在宿主巨噬細胞內複製