Antimicrobial Activity of Trigonelline Hydrochloride Against Pseudomonas aeruginosa and Its Quorum-Sensing Regulated Molecular Mechanisms on Biofilm Formation and Virulence

IF 3.8 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2024-01-17 DOI:10.1021/acsinfecdis.3c00617

Amiya Kar, Samir Kumar Mukherjee, Subhasis Barik and Sk Tofajjen Hossain*,

{"title":"Antimicrobial Activity of Trigonelline Hydrochloride Against Pseudomonas aeruginosa and Its Quorum-Sensing Regulated Molecular Mechanisms on Biofilm Formation and Virulence","authors":"Amiya Kar, Samir Kumar Mukherjee, Subhasis Barik and Sk Tofajjen Hossain*, ","doi":"10.1021/acsinfecdis.3c00617","DOIUrl":null,"url":null,"abstract":"Pseudomonas aeruginosa, a vivid biofilm-producing bacterium, is considered a dreadful opportunistic pathogen, and thus, management of biofilm-associated infections due to multidrug resistant strains by traditional drugs currently is of great concern. This study was aimed to assess the impact of trigonelline hydrochloride, a pyridine alkaloid, on P. aeruginosa PAO1, in search of an alternative therapeutant. The effect of trigonelline on colony morphology and motility was studied along with its role on biofilm and expression virulence factors. Trigonelline influenced the colony structure, motility, biofilm architecture, and the production of virulence factors in a dose-dependent manner. Alterations in quorum sending (QS)-regulated gene expression after treatment and molecular docking analysis for certain regulator proteins confirmed its effect on the QS-system network by affecting Las, Rhl, and Pqs signaling pathways and as possible molecular targets. Thus, trigonelline might be considered as a potential chemical lead to manage biofilm-associated pathogenesis or to develop other analogues with enhanced pharmacokinetic actions.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":"10 2","pages":"746–762"},"PeriodicalIF":3.8000,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsinfecdis.3c00617","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Pseudomonas aeruginosa, a vivid biofilm-producing bacterium, is considered a dreadful opportunistic pathogen, and thus, management of biofilm-associated infections due to multidrug resistant strains by traditional drugs currently is of great concern. This study was aimed to assess the impact of trigonelline hydrochloride, a pyridine alkaloid, on P. aeruginosa PAO1, in search of an alternative therapeutant. The effect of trigonelline on colony morphology and motility was studied along with its role on biofilm and expression virulence factors. Trigonelline influenced the colony structure, motility, biofilm architecture, and the production of virulence factors in a dose-dependent manner. Alterations in quorum sending (QS)-regulated gene expression after treatment and molecular docking analysis for certain regulator proteins confirmed its effect on the QS-system network by affecting Las, Rhl, and Pqs signaling pathways and as possible molecular targets. Thus, trigonelline might be considered as a potential chemical lead to manage biofilm-associated pathogenesis or to develop other analogues with enhanced pharmacokinetic actions.

Abstract Image

查看原文本刊更多论文

盐酸川芎嗪对铜绿假单胞菌的抗菌活性及其对生物膜形成和毒性的法定量感应调控分子机制

铜绿假单胞菌是一种生动的产生生物膜的细菌，被认为是一种可怕的机会性病原体，因此，用传统药物治疗多药耐药菌株引起的生物膜相关感染目前备受关注。本研究旨在评估吡啶生物碱盐酸三尖杉酯碱对铜绿假单胞菌 PAO1 的影响，以寻找替代治疗药物。研究了三尖杉酯碱对菌落形态和运动的影响，以及它对生物膜和毒力因子表达的作用。三尖杉酯碱以剂量依赖的方式影响菌落结构、运动性、生物膜结构和毒力因子的产生。处理后法定量发送（QS）调控基因表达的改变以及某些调控蛋白的分子对接分析证实，三高宁通过影响 Las、Rhl 和 Pqs 信号通路对 QS 系统网络产生影响，并可能成为分子靶标。因此，三尖杉酯碱可被视为一种潜在的化学线索，用于控制与生物膜相关的致病机理或开发其他具有更强药代动力学作用的类似物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.