Brucella secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysis
Increased glycolytic metabolism is a key step in the reproduction of Brucella and the induction of brucellosis, however, little is known about how this process is regulated during infection. Forkhead box protein O1 (FOXO1) is a transcription factor that regulates energy metabolism. In this study, we...
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China Science Publishing & Media Ltd.
2024-11-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024203 |
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| author | Cao Shuzhu Han Xinxin Deng Xingmei Guo Jia Liu Liangbo Zhang Yu Suleimenov Maratbek Zhao Tianyi Li Wei Ding Jian Xie Songsong Zhang Hui |
| author_facet | Cao Shuzhu Han Xinxin Deng Xingmei Guo Jia Liu Liangbo Zhang Yu Suleimenov Maratbek Zhao Tianyi Li Wei Ding Jian Xie Songsong Zhang Hui |
| author_sort | Cao Shuzhu |
| collection | DOAJ |
| description | Increased glycolytic metabolism is a key step in the reproduction of Brucella and the induction of brucellosis, however, little is known about how this process is regulated during infection. Forkhead box protein O1 (FOXO1) is a transcription factor that regulates energy metabolism. In this study, we employ the yeast two-hybrid system (Y2H) and immunoprecipitation (Co-IP) to reverse screen for the FOXO1 for the first time and identify interactions between FOXO1 and the Brucella secretory protein VceA. Our findings reveal that the Brucella secretory protein VceA colocalizes with FOXO1 in the cytoplasm. Additionally, we observe that infection of macrophages with Brucella abortus 2308 ( S2308) promotes FOXO1 entry into the nucleus, leading to a significant upregulation of glycolysis level in macrophage. Conversely, in a VceA mutant strain (S2308-ΔVceA), we note a significant reduction in the ability of FOXO1 to enter the nucleus, accompanied by a decrease in glycolysis level. Furthermore, Brucella interacts with FOXO1 through the secreted protein VceA, promoting the entry of FOXO1 into the nucleus and thereby altering host metabolic patterns. This study provides insights into the mechanisms by which Brucella invades host macrophages and induces unique metabolic changes. These insights may offer a novel rationale for developing metabolic therapeutic strategies for the treatment and prevention of related diseases. |
| format | Article |
| id | doaj-art-3d0e85efb9914359b2068bb6f4b91db1 |
| institution | OA Journals |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-3d0e85efb9914359b2068bb6f4b91db12025-08-20T02:34:39ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-11-015780581710.3724/abbs.202420320d259ccBrucella secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysisCao Shuzhu0Han Xinxin1Deng Xingmei2Guo Jia3Liu Liangbo4Zhang Yu5Suleimenov Maratbek6Zhao Tianyi7Li Wei8Ding Jian9Xie Songsong10Zhang Hui11["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"]["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"]["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"]["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"]["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"]["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"]["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China","College of Veterinary, National Agricultural University of Kazakhstan, Nur Sultan, Kazakhstan"]["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"]["Xinjiang Center for Animal Disease Prevention and Control, Urumqi 830000, China"]["Xinjiang Center for Animal Disease Prevention and Control, Urumqi 830000, China"]["NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital of Shihezi University, Shihezi 832008, China"]["State International Joint Research Center for Animal Health Breeding, College of Animal Science and Technology, Shihezi University, Shihezi 832003, China"]Increased glycolytic metabolism is a key step in the reproduction of Brucella and the induction of brucellosis, however, little is known about how this process is regulated during infection. Forkhead box protein O1 (FOXO1) is a transcription factor that regulates energy metabolism. In this study, we employ the yeast two-hybrid system (Y2H) and immunoprecipitation (Co-IP) to reverse screen for the FOXO1 for the first time and identify interactions between FOXO1 and the Brucella secretory protein VceA. Our findings reveal that the Brucella secretory protein VceA colocalizes with FOXO1 in the cytoplasm. Additionally, we observe that infection of macrophages with Brucella abortus 2308 ( S2308) promotes FOXO1 entry into the nucleus, leading to a significant upregulation of glycolysis level in macrophage. Conversely, in a VceA mutant strain (S2308-ΔVceA), we note a significant reduction in the ability of FOXO1 to enter the nucleus, accompanied by a decrease in glycolysis level. Furthermore, Brucella interacts with FOXO1 through the secreted protein VceA, promoting the entry of FOXO1 into the nucleus and thereby altering host metabolic patterns. This study provides insights into the mechanisms by which Brucella invades host macrophages and induces unique metabolic changes. These insights may offer a novel rationale for developing metabolic therapeutic strategies for the treatment and prevention of related diseases.https://www.sciengine.com/doi/10.3724/abbs.2024203<italic>Brucella abortus</italic>VceAFOXO1glycolysis |
| spellingShingle | Cao Shuzhu Han Xinxin Deng Xingmei Guo Jia Liu Liangbo Zhang Yu Suleimenov Maratbek Zhao Tianyi Li Wei Ding Jian Xie Songsong Zhang Hui Brucella secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysis Acta Biochimica et Biophysica Sinica <italic>Brucella abortus</italic> VceA FOXO1 glycolysis |
| title | Brucella secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysis |
| title_full | Brucella secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysis |
| title_fullStr | Brucella secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysis |
| title_full_unstemmed | Brucella secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysis |
| title_short | Brucella secretory protein VceA promotes FOXO1 entry into the nucleus to shift host cell metabolism toward glycolysis |
| title_sort | brucella secretory protein vcea promotes foxo1 entry into the nucleus to shift host cell metabolism toward glycolysis |
| topic | <italic>Brucella abortus</italic> VceA FOXO1 glycolysis |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024203 |
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