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, Jin Chen, Qian Wang, Hongmin Sun, Qing Li, Zhen Chen, Jingliang Qin, Jianwei Mu, Bin Liu, Qiyue Zhang, Yutao Liu, Lu Feng, Lei Wang
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. Here, Li et al. report a two-component system, GrpP/GrpQ, which promotes UPEC pathogenicity. Mechanistically, GrpP/GrpQ directly activates type 1 fimbria expression to promote UPEC invasion in response to D-serine in the host urine.