{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:44:03Z","timestamp":1760150643602,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T00:00:00Z","timestamp":1701907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31970179","32170199"],"award-info":[{"award-number":["31970179","32170199"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Salmonella enterica serovar Typhimurium (S. Typhimurium), an important foodborne pathogen, causes diarrheal illness and gastrointestinal diseases. S. Typhimurium survives and replicates in phagocytic and non-phagocytic cells for acute or chronic infections. In these cells, S. Typhimurium resides within Salmonella-containing vacuoles (SCVs), in which the phosphate (Pi) concentration is low. S. Typhimurium senses low Pi and expresses virulence factors to modify host cells. However, the mechanism by which host cells reduce the Pi concentration in SCVs is not clear. In this study, we show that through the TLR4-MyD88-NF-\u03baB signaling pathway, S. Typhimurium upregulates PIT1, which in turn transports Pi from SCVs into the cytosol and results in Pi starvation in SCVs. Immunofluorescence and western blotting analysis reveal that after the internalization of S. Typhimurium, PIT1 is located on SCV membranes. Silencing or overexpressing PIT1 inhibits or promotes Pi starvation, Salmonella pathogenicity island-2 (SPI-2) gene expression, and replication in SCVs. The S. Typhimurium \u0394msbB mutant or silenced TLR4-MyD88-NF-\u03baB pathway suppresses the expression of the SPI-2 genes and promotes the fusion of SCVs with lysosomes. Our results illustrate that S. Typhimurium exploits the host innate immune responses as signals to promote intracellular replication, and they provide new insights for the development of broad-spectrum therapeutics to combat bacterial infections.<\/jats:p>","DOI":"10.3390\/ijms242417216","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T03:35:31Z","timestamp":1701920131000},"page":"17216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phosphate (Pi) Transporter PIT1 Induces Pi Starvation in Salmonella-Containing Vacuole in HeLa Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Wen","family":"Yang","sequence":"first","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China"},{"name":"TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingxing","family":"Feng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China"},{"name":"Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yan","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China"},{"name":"TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenbo","family":"Kang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China"},{"name":"TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Yao","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China"},{"name":"TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongmin","family":"Sun","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China"},{"name":"TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihui","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University, Tianjin 300071, China"},{"name":"Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/nrmicro1788","article-title":"Salmonellae interplay with host cells","volume":"6","author":"Haraga","year":"2008","journal-title":"Nat. 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