Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophages
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 i...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/103714 |
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| author | Shuai Ma Bin Yang Yuyang Sun Xinyue Wang Houliang Guo Ruiying Liu Ting Ye Chenbo Kang Jingnan Chen Lingyan Jiang |
| author_facet | Shuai Ma Bin Yang Yuyang Sun Xinyue Wang Houliang Guo Ruiying Liu Ting Ye Chenbo Kang Jingnan Chen Lingyan Jiang |
| author_sort | Shuai Ma |
| collection | DOAJ |
| description | 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 partially 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. |
| format | Article |
| id | doaj-art-2f9f2e01978947aba3fa86901a52f8be |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-2f9f2e01978947aba3fa86901a52f8be2025-08-20T03:31:16ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011310.7554/eLife.103714Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophagesShuai Ma0https://orcid.org/0009-0006-8348-0805Bin Yang1Yuyang Sun2Xinyue Wang3Houliang Guo4Ruiying Liu5Ting Ye6Chenbo Kang7Jingnan Chen8Lingyan Jiang9https://orcid.org/0000-0001-8580-606XNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai University, Tianjin, ChinaSalmonella 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 partially 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.https://elifesciences.org/articles/103714Salmonellareplication in macrophagevirulenceβ-alaninezinc uptake |
| spellingShingle | Shuai Ma Bin Yang Yuyang Sun Xinyue Wang Houliang Guo Ruiying Liu Ting Ye Chenbo Kang Jingnan Chen Lingyan Jiang Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophages eLife Salmonella replication in macrophage virulence β-alanine zinc uptake |
| title | Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophages |
| title_full | Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophages |
| title_fullStr | Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophages |
| title_full_unstemmed | Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophages |
| title_short | Salmonella exploits host- and bacterial-derived β-alanine for replication inside host macrophages |
| title_sort | salmonella exploits host and bacterial derived β alanine for replication inside host macrophages |
| topic | Salmonella replication in macrophage virulence β-alanine zinc uptake |
| url | https://elifesciences.org/articles/103714 |
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