群体感应抑制对尿路致病性大肠杆菌的影响。

Impact of long-term quorum sensing inhibition on uropathogenic Escherichia coli.

机构信息

Biomolecular Sciences Research Centre, Sheffield Hallam University, Sheffield, UK.

Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.

出版信息

J Antimicrob Chemother. 2021 Mar 12;76(4):909-919. doi: 10.1093/jac/dkaa517.

DOI:10.1093/jac/dkaa517

PMID:33406232

Abstract

BACKGROUND

Quorum sensing is an extracellular bacterial communication system used in the density-dependent regulation of gene expression and development of biofilms. Biofilm formation has been implicated in the establishment of catheter-associated urinary tract infections and therefore quorum sensing inhibitors (QSIs) have been suggested as anti-biofilm catheter coating agents. The long-term effects of QSIs in uropathogens is, however, not clearly understood.

OBJECTIVES

We evaluated the effects of repeated exposure to the QSIs cinnamaldehyde, (Z)-4-bromo-5(bromomethylene)-2(5H)-furanone-C30 (furanone-C30) and 4-fluoro-5-hydroxypentane-2,3-dione (F-DPD) on antimicrobial susceptibility, biofilm formation and relative pathogenicity in eight uropathogenic Escherichia coli (UPEC) isolates.

METHODS

MICs, MBCs and minimum biofilm eradication concentrations and antibiotic susceptibility were determined. Biofilm formation was quantified using crystal violet. Relative pathogenicity was assessed in a Galleria mellonella model. To correlate changes in phenotype to gene expression, transcriptomic profiles were created through RNA sequencing and variant analysis of genomes was performed in strain EC958.

RESULTS

Cinnamaldehyde and furanone-C30 led to increases in susceptibility in planktonic and biofilm-associated UPEC. Relative pathogenicity increased after cinnamaldehyde exposure (4/8 isolates), decreased after furanone-C30 exposure (6/8 isolates) and varied after F-DPD exposure (one increased and one decreased). A total of 9/96 cases of putative antibiotic cross-resistance were generated. Exposure to cinnamaldehyde or F-DPD reduced expression of genes associated with locomotion, whilst cinnamaldehyde caused an increase in genes encoding fimbrial and afimbrial-like adhesins. Furanone-C30 caused a reduction in genes involved in cellular biosynthetic processes, likely though impaired ribonucleoprotein assembly.

CONCLUSIONS

The multiple phenotypic adaptations induced during QSI exposure in UPEC should be considered when selecting an anti-infective catheter coating agent.

摘要

背景

群体感应是一种细菌细胞外通讯系统，用于基因表达和生物膜发育的密度依赖性调节。生物膜形成与导管相关尿路感染的建立有关，因此群体感应抑制剂（QSIs）被认为是抗生物膜导管涂层剂。然而，尿路病原体中 QSIs 的长期影响尚不清楚。

目的

我们评估了反复接触肉桂醛、（Z）-4-溴-5（溴亚甲基）-2（5H）-呋喃酮-C30（呋喃酮-C30）和 4-氟-5-羟基戊烷-2,3-二酮（F-DPD）对 8 株尿路致病性大肠杆菌（UPEC）分离株的抗菌敏感性、生物膜形成和相对致病性的影响。

方法

测定 MIC、MBC 和最低生物膜清除浓度以及抗生素敏感性。使用结晶紫定量测定生物膜形成。在大蜡螟模型中评估相对致病性。为了将表型变化与基因表达相关联，通过 RNA 测序创建转录组图谱，并在 EC958 菌株中进行基因组变体分析。

结果

肉桂醛和呋喃酮-C30 导致浮游生物和生物膜相关 UPEC 的敏感性增加。肉桂醛暴露后相对致病性增加（8 株中有 4 株），呋喃酮-C30 暴露后相对致病性降低（8 株中有 6 株），F-DPD 暴露后相对致病性变化（1 株增加，1 株减少）。总共产生了 9/96 例潜在的抗生素交叉耐药病例。肉桂醛或 F-DPD 的暴露降低了与运动相关的基因表达，而肉桂醛导致菌毛和非菌毛样黏附素编码基因的增加。呋喃酮-C30 导致参与细胞生物合成过程的基因减少，可能是通过核糖核蛋白组装受损。