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Here, we found that either acquisition from the host or de novo synthesis of a nonprotein amino acid, \u03b2-alanine, is critical for\n                    <jats:italic>Salmonella<\/jats:italic>\n                    replication inside macrophages. The concentration of \u03b2-alanine is decreased in\n                    <jats:italic>Salmonella<\/jats:italic>\n                    -infected macrophages, while the addition of exogenous \u03b2-alanine enhances\n                    <jats:italic>Salmonella<\/jats:italic>\n                    replication in macrophages, suggesting that\n                    <jats:italic>Salmonella<\/jats:italic>\n                    can uptake host-derived \u03b2-alanine for intracellular growth. Moreover, the expression of\n                    <jats:italic>panD,<\/jats:italic>\n                    the rate-limiting gene required for \u03b2-alanine synthesis in\n                    <jats:italic>Salmonella,<\/jats:italic>\n                    is upregulated when\n                    <jats:italic>Salmonella<\/jats:italic>\n                    enters macrophages. Mutation of\n                    <jats:italic>panD<\/jats:italic>\n                    impaired\n                    <jats:italic>Salmonella<\/jats:italic>\n                    replication in macrophages and colonization in the mouse liver and spleen, indicating that de novo synthesis of \u03b2-alanine is essential for intracellular\n                    <jats:italic>Salmonella<\/jats:italic>\n                    growth and systemic infection. Additionally, we revealed that \u03b2-alanine influences\n                    <jats:italic>Salmonella<\/jats:italic>\n                    intracellular replication and in vivo virulence partially by increasing expression of the zinc transporter genes\n                    <jats:italic>znuABC<\/jats:italic>\n                    , which in turn facilitates the uptake of the essential micronutrient zinc by\n                    <jats:italic>Salmonella<\/jats:italic>\n                    . Taken together, these findings highlight the important role of \u03b2-alanine in the intracellular replication and virulence of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    , and\n                    <jats:italic>panD<\/jats:italic>\n                    is a promising target for controlling systemic\n                    <jats:italic>Salmonella<\/jats:italic>\n                    infection.\n                  <\/jats:p>","DOI":"10.7554\/elife.103714","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T04:25:22Z","timestamp":1732163122000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.103714","source":"Crossref","is-referenced-by-count":4,"title":["Salmonella exploits host- and bacterial-derived \u03b2-alanine for replication inside host macrophages"],"prefix":"10.7554","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8348-0805","authenticated-orcid":true,"given":"Shuai","family":"Ma","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01y1kjr75","id-type":"ROR","asserted-by":"publisher"}],"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University","place":["Tianjin, 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