Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria
Abstract Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTIs). Invasion into bladder epithelial cells (BECs) on the bladder luminal surface via type 1 fimbria is the first critical step in UPEC infection. Although type 1 fimbria expression increases during UPEC i...
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| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-55982-z |
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| _version_ | 1841544443790884864 |
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| author | Xueping Li Yu Pang Lingyan Jiang Le Liu Jiarui Zhou Chen Jin Qian Wang Hongmin Sun Qing Li Zhen Chen Jingliang Qin Jianwei Mu Bin Liu Qiyue Zhang Yutao Liu Lu Feng Lei Wang |
| author_facet | Xueping Li Yu Pang Lingyan Jiang Le Liu Jiarui Zhou Chen Jin Qian Wang Hongmin Sun Qing Li Zhen Chen Jingliang Qin Jianwei Mu Bin Liu Qiyue Zhang Yutao Liu Lu Feng Lei Wang |
| author_sort | Xueping Li |
| collection | DOAJ |
| description | Abstract Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTIs). Invasion into bladder epithelial cells (BECs) on the bladder luminal surface via type 1 fimbria is the first critical step in UPEC infection. Although type 1 fimbria expression increases during UPEC invasion of BECs, the underlying regulatory mechanisms remain poorly understood. This study reported a previously uncharacterized two-component system (TCS) GrpP/GrpQ that directly activates type 1 fimbria expression to promote UPEC invasion and therefore pathogenicity in response to D-serine present in the host urine. grpP/grpQ mutation severely impaired UPEC invasion of BECs and decreased the bacterial burden and formation of intracellular bacterial communities in mouse bladders during acute UTI. grpP/grpQ is widely present in UPEC genomes but rarely in other E. coli genomes, suggesting that this TCS specifically contributes to UPEC evolution. This study revealed a new pathway for virulence activation in response to host cues, providing further insight into UPEC pathogenesis and a promising target for UTI treatment. |
| format | Article |
| id | doaj-art-7e3ae2113b694e66860c6c25551a0cfd |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-7e3ae2113b694e66860c6c25551a0cfd2025-01-12T12:32:00ZengNature PortfolioNature Communications2041-17232025-01-0116111610.1038/s41467-025-55982-zTwo-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbriaXueping Li0Yu Pang1Lingyan Jiang2Le Liu3Jiarui Zhou4Chen Jin5Qian Wang6Hongmin Sun7Qing Li8Zhen Chen9Jingliang Qin10Jianwei Mu11Bin Liu12Qiyue Zhang13Yutao Liu14Lu Feng15Lei Wang16National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, TEDA Institute of Biological Sciences and Biotechnology, Nankai UniversityAbstract Uropathogenic Escherichia coli (UPEC) is a major cause of urinary tract infections (UTIs). Invasion into bladder epithelial cells (BECs) on the bladder luminal surface via type 1 fimbria is the first critical step in UPEC infection. Although type 1 fimbria expression increases during UPEC invasion of BECs, the underlying regulatory mechanisms remain poorly understood. This study reported a previously uncharacterized two-component system (TCS) GrpP/GrpQ that directly activates type 1 fimbria expression to promote UPEC invasion and therefore pathogenicity in response to D-serine present in the host urine. grpP/grpQ mutation severely impaired UPEC invasion of BECs and decreased the bacterial burden and formation of intracellular bacterial communities in mouse bladders during acute UTI. grpP/grpQ is widely present in UPEC genomes but rarely in other E. coli genomes, suggesting that this TCS specifically contributes to UPEC evolution. This study revealed a new pathway for virulence activation in response to host cues, providing further insight into UPEC pathogenesis and a promising target for UTI treatment.https://doi.org/10.1038/s41467-025-55982-z |
| spellingShingle | Xueping Li Yu Pang Lingyan Jiang Le Liu Jiarui Zhou Chen Jin Qian Wang Hongmin Sun Qing Li Zhen Chen Jingliang Qin Jianwei Mu Bin Liu Qiyue Zhang Yutao Liu Lu Feng Lei Wang Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria Nature Communications |
| title | Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria |
| title_full | Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria |
| title_fullStr | Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria |
| title_full_unstemmed | Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria |
| title_short | Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria |
| title_sort | two component system grpp grpq promotes pathogenicity of uropathogenic escherichia coli cft073 by upregulating type 1 fimbria |
| url | https://doi.org/10.1038/s41467-025-55982-z |
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