AUTHOR=Zhang Si , Wang Jingting , Fan Yu , Meng Wang , Qian Chengqian , Liu Peng , Wei Yi , Yuan Chao , Du Yuhui , Yin Zhiqiu 

TITLE=YciR, a Specific 3′-Phosphodiesterase, Plays a Role in the Pathogenesis of Uropathogenic Escherichia coli CFT073

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.910906

DOI=10.3389/fmicb.2022.910906

ISSN=1664-302X

ABSTRACT=Urinary tract infections (UTIs), with a characteristic of recurrence and resistance to antibiotics due to misuse, remain a common health and economic issue for patients. Uropathogenic Escherichia coli (UPEC), which is capable of evading immune response by forming intracellular bacterial communities (IBCs) in the cytoplasm of bladder epithelial cells (BECs) after the invasion, is proved to be a prevailing cause of UTIs. Cyclic dimeric guanosine monophosphate (c-di-GMP) is a small molecule responsible for eliciting the innate immune response of the host only if it has not been degraded by some phosphodiesterases such as YciR. The relationship between YciR and c-di-GMP level is inconclusive in UPEC. In this study, we investigated the gene expression profile of UPEC in BECs and identified yciR as an up-regulated gene. Western Blot revealed that YciR enhances the virulence of UPEC by inhibiting the phosphorylation of NF-κB. It is also exhibited that the expression of yciR could be repressed by HupB in a directly binding manner. We found YciR, a novel PDE, and defined its possible function in innate immune evasion. We also demonstrated that YciR is a HupB-dependent PDE that degrades c-di-GMP and that a low concentration of c-di-GMP might make NF-κB less phosphorylated, reducing the host's pro-inflammation. This is the first time that YciR has been identified as a virulence factor in the pathogenesis of UPEC. These findings further increase the understanding of the pathogenesis of UPEC and provide a theoretical basis for further studies.