背景:尿路感染是最常见的医院和社区获得性感染之一,尿路致病性大肠杆菌(UPEC)是主要病原体。全球多药耐药(MDR)UPEC的出现增加需要探索新的方法。如今,将天然产物重新用作抗群体感应(QS)剂以阻止细菌毒力的势头正在增强。因此,这项研究调查了香芹酚的抗QS电位,肉桂醛,和丁香酚对从埃及患者尿液培养物中分离的大肠杆菌。
结果:对67个大肠杆菌分离株进行了抗生素敏感性测试,94%的分离株显示MDR表型。使用PCR检测usp基因,45%的分离株被归类为UPEC。植物化学品,在它们的亚抑制浓度下,抑制UPEC分离株的游泳和抽搐活动,其中丁香酚表现出最高的抑制作用。这些试剂阻碍了测试分离物的生物膜形成能力,在两个温度集下,37和30°C,其中丁香酚在两个研究温度下成功地显著抑制生物膜形成>50%,与未处理的对照相比。植物化学物质被证明下调QS基因(luxS)和与运动性相关的关键基因的表达,断言他们的反QS潜力。Further,植物产品与5种抗生素的组合活性通过棋盘法进行评估。植物产品的添加显著降低了抗生素的最低抑制浓度,并产生了几种协同或部分协同的组合。其中一些以前没有被探索过。
结论:总体而言,香芹酚,肉桂醛,丁香酚可以作为潜在的抗QS药物,其优先减少基于QS的通信并减弱基因表达的级联,从而减少UPEC中毒力因子的产生,最终,消退他们的致病性。此外,这些药物与抗生素的协同组合可能为规避高抗生素剂量带来的副作用提供了新的视角,从而为克服抗生素耐药性铺平了道路。
Urinary tract infections represent one of the most frequent hospital and community-acquired infections with uropathogenic Escherichia coli (UPEC) being the main causative agent. The global increase in the emergence of multidrug-resistant (MDR) UPEC necessitates exploring novel approaches. Repurposing natural products as anti-quorum sensing (QS) agents to impede bacterial virulence is gaining momentum nowadays. Hence, this study investigates the anti-QS potentials of carvacrol, cinnamaldehyde, and eugenol against E. coli isolated from urine cultures of Egyptian patients.
Antibiotic susceptibility testing was performed for 67 E. coli isolates and 94% of the isolates showed MDR phenotype. The usp gene was detected using PCR and accordingly, 45% of the isolates were categorized as UPEC. Phytochemicals, at their sub-inhibitory concentrations, inhibited the swimming and twitching motilities of UPEC isolates, with eugenol showing the highest inhibitory effect. The agents hindered the biofilm-forming ability of the tested isolates, at two temperature sets, 37 and 30 °C, where eugenol succeeded in significantly inhibiting the biofilm formation by > 50% at both investigated temperatures, as compared with untreated controls. The phytochemicals were shown to downregulate the expression of the QS gene (luxS) and critical genes related to motility, asserting their anti-QS potential. Further, the combinatory activity of the phytoproducts with five antibiotics was assessed by checkerboard assay. The addition of the phytoproducts significantly reduced the minimum inhibitory concentrations of the antibiotics and generated several synergistic or partially synergistic combinations, some of which have not been previously explored.
Overall, carvacrol, cinnamaldehyde, and eugenol could be repurposed as potential anti-QS agents, which preferentially reduce the QS-based communication and attenuate the cascades of gene expression, thus decreasing the production of virulence factors in UPEC, and eventually, subsiding their pathogenicity. Furthermore, the synergistic combinations of these agents with antibiotics might provide a new perspective to circumvent the side effects brought about by high antibiotic doses, thereby paving the way for overcoming antibiotic resistance.