Two-component system GrpP/GrpQ promotes pathogenicity of uropathogenic Escherichia coli CFT073 by upregulating type 1 fimbria

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 () and Lei Wang ()
Additional contact information
Xueping Li: Nankai University
Yu Pang: Nankai University
Lingyan Jiang: Nankai University
Le Liu: Nankai University
Jiarui Zhou: Nankai University
Chen Jin: Nankai University
Qian Wang: Nankai University
Hongmin Sun: Nankai University
Qing Li: Nankai University
Zhen Chen: Nankai University
Jingliang Qin: Nankai University
Jianwei Mu: Nankai University
Bin Liu: Nankai University
Qiyue Zhang: Nankai University
Yutao Liu: Nankai University
Lu Feng: Nankai University
Lei Wang: Nankai University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-55982-z

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