Institute of Science, Nirma University, Ahmedabad- 382481, India.
National Institute of Ayurveda, Jaipur, India.
Curr Drug Discov Technol. 2021;18(3):391-404. doi: 10.2174/1568009620666200421083120.
Antibiotic-resistant members of the family Enterobacteriaceae are among the serious threats to human health globally. This study reports the anti-pathogenic activity of Punica granatum peel extract (PGPE) against a multi-drug resistant, beta-lactamase producing member of this family i.e. Serratia marcescens.
This study aimed at assessing the anti-pathogenic activity of PGPE against the gramnegative bacterial pathogen S. marcescens and identifying the molecular targets of this extract in the test bacterium.
Effect of PGPE on S. marcescens growth and quorum sensing (QS)-regulated pigment production was assessed through broth dilution assay. In vivo anti-infective and prophylactic activity of PGPE was assessed employing the nematode worm Caenorhabditis elegans as a model host. Differential gene expression in PGPE-exposed S. marcescens was studied through a whole transcriptome approach.
PGPE was able to modulate QS-regulated pigment production in S. marcescens without exerting any heavy growth-inhibitory effect at concentrations as low as ≥2.5 μg/mL. It could attenuate the virulence of the test bacterium towards the worm host by 22-42% (p≤0.01) at even lower concentrations (≥0.5 μg/mL). PGPE also exerted a post-extract effect on S. marcescens. This extract was found to offer prophylactic benefit too, to the host worm, as PGPE-pre-fed worms scored better (34-51%; p≤0.001) survival in face of subsequent bacterial attack. Differential gene expression analysis revealed that PGPE affected the expression of a total of 66 genes in S. marcescens by ≥1.5 fold.
The anti-virulence effect of PGPE against S. marcescens is multifaceted, affecting stress-response machinery, efflux activity, iron homeostasis, and cellular energetics of this bacterium notably. Among the major molecular targets identified in this study are LPS export transporter permease (LptF), t-RNA pseudouridine synthase (TruB), etc.
肠杆菌科的抗生素耐药成员是全球人类健康的严重威胁之一。本研究报告了石榴皮提取物（PGPE）对该家族产β-内酰胺酶的多药耐药成员即粘质沙雷氏菌的抗病原活性。
本研究旨在评估 PGPE 对革兰氏阴性细菌病原体粘质沙雷氏菌的抗病原活性，并确定该提取物在测试细菌中的分子靶标。
通过肉汤稀释法评估 PGPE 对粘质沙雷氏菌生长和群体感应（QS）调节色素产生的影响。使用秀丽隐杆线虫作为模型宿主评估 PGPE 的体内抗感染和预防活性。通过全转录组方法研究 PGPE 暴露的粘质沙雷氏菌中的差异基因表达。
PGPE 能够在不产生任何明显生长抑制作用的情况下，以低至≥2.5μg/ml 的浓度调节粘质沙雷氏菌的 QS 调节色素产生。它可以通过在更低的浓度（≥0.5μg/ml）下使测试细菌对蠕虫宿主的毒力降低 22-42%（p≤0.01）。PGPE 还对粘质沙雷氏菌产生了后提取物效应。该提取物还为宿主蠕虫提供了预防益处，PGPE 预先喂养的蠕虫在随后的细菌攻击中表现出更好的（34-51%；p≤0.001）存活率。差异基因表达分析显示，PGPE 以≥1.5 倍的幅度影响了粘质沙雷氏菌中总共 66 个基因的表达。
PGPE 对粘质沙雷氏菌的抗毒力作用是多方面的，显著影响了该细菌的应激反应机制、外排活性、铁稳态和细胞能量学。本研究中确定的主要分子靶标包括 LPS 外排转运体通透酶（LptF）、t-RNA 假尿嘧啶合酶（TruB）等。
