The DanRI regulatory system in uropathogenic Escherichia coli subverts neutrophil responses

IF 18.7 1区医学 Q1 MICROBIOLOGY

Cell host & microbe Pub Date : 2026-03-30 DOI:10.1016/j.chom.2026.03.013

Dora Čerina, Matthieu Rousseau, Carla Hart Olaiz, Gerben Marsman, Arturo Zychlinsky, Molly A. Ingersoll

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Abstract

Uropathogenic Escherichia coli (UPEC) is the primary cause of urinary tract infections (UTIs). To establish an infection, UPEC must evade infiltrating neutrophils and their antimicrobial neutrophil extracellular traps (NETs). In this study, we identify a previously uncharacterized two-gene regulatory system within the pathogenicity island PAI_UTI89II, which we named DanRI (defense against neutrophil regulator and inhibitor). DanRI is induced by nucleosomes present in NETs and enables UPEC to suppress neutrophil responses by attenuating reactive oxygen species production and subsequent NET formation. Mechanistically, DanI functions as an antagonist to the transcriptional regulator DanR, thereby modulating key bacterial processes, including metabolic, flagellar biosynthesis, and stress response pathways. DanRI enhances UPEC fitness by dampening the early host inflammatory response during UTI in a mouse model. Taken together, these findings reveal DanRI as a regulatory system that promotes UPEC pathogenesis by facilitating immune evasion.

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尿路致病性大肠杆菌中的DanRI调控系统破坏中性粒细胞反应

尿路致病性大肠杆菌（UPEC）是尿路感染（uti）的主要原因。为了建立感染，upc必须避开浸润的中性粒细胞及其抗菌中性粒细胞胞外陷阱（NETs）。在这项研究中，我们在致病性岛屿PAIUTI89II中发现了一个以前未被描述的双基因调控系统，我们将其命名为DanRI（防御中性粒细胞调节剂和抑制剂）。DanRI由NET中存在的核小体诱导，并使UPEC通过减弱活性氧的产生和随后的NET形成来抑制中性粒细胞反应。从机制上讲，DanI作为转录调节因子DanR的拮抗剂，从而调节关键的细菌过程，包括代谢、鞭毛生物合成和应激反应途径。在小鼠模型中，DanRI通过抑制UTI期间的早期宿主炎症反应来增强upc适应性。综上所述，这些发现表明DanRI是一个通过促进免疫逃避促进UPEC发病的调控系统。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell host & microbe 生物-微生物学

CiteScore

45.10

自引率

1.70%

发文量

201

审稿时长

4-8 weeks

期刊介绍： Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.