Fakhar Maryum, Ahmed Mehboob, Nasim Sabri Anjum
Institute of Microbiology and Molecular Genetics, Quaid-e-Azam Campus, University of the Punjab, Lahore 54590, Pakistan.
Saudi J Biol Sci. 2024 Jun;31(6):104001. doi: 10.1016/j.sjbs.2024.104001. Epub 2024 Apr 16.
is a Gram-negative opportunistic bacterium, ubiquitously found in nature and causative agent in many infections. Due to increased antibiotic resistance, there is a need to develop more robust antibacterial agents from natural sources. In this study, we worked on two metallo-β-lactamase (MBL) producing strains and targeted the Quorum Sensing mechanism (QS) of these bacteria to combat antibiotic resistance. Our study aimed at using phytochemicals which have been used since centuries in herbal medicine. We used fifteen commercially available phytochemicals and check their effects on biofilm formation, quorum sensing and inter-related mechanisms. Sub-inhibitory concentration of isoliquiritin inhibited biofilm formation 55 % in P8 at day 6 and 48 % in P6 at day 6; quorum sensing 83 % in P6 and 61 % in P8 whereas sub-inhibitory concentration of 6-gingerol suppressed biofilm formation by 48 % in P8 at day 6 and 44 % in P6 at day 6; quorum sensing 69 % in P6 and 48 % in P8, respectively. The results indicated isoliquiritin, epigallocatechin gallate, eugenol, luteolin and chrysin to be the potential candidates in inhibiting QS and related mechanisms. Isoliquiritin which was never been used before against biofilm and QS related studies, showed remarkable results and found to be more efficient in inhibiting QS than 6-gingerol -a known QS inhibitor. For examining the molecular interaction between phytochemicals and QS, In-silico molecular docking was performed between phytoligands and four QS proteins (). docking analysis revealed that isoliquiritin showed strong bond with amino acids (Trp34, Asp35, Asp35, Tyr105, Arg104, Val138, Thr140) present at the active site of RhlI with binding energy value of -8.4 kcal/mol as compared to that of 6-gingerol with Rhl1 (-7.3 kcal/mol). In conclusion, our study may help in controlling nosocomial infections caused by carbapenem-resistant metallo beta-lactamase (MBL-PA) by utilizing these phytochemicals in biofilms disruption and quorum sensing inhibition. Moreover their synergism with antibiotics may help in lowering the MIC of carbapenem antibiotics against such Multi-drug resistant strains.
是一种革兰氏阴性机会致病菌，广泛存在于自然界，是多种感染的病原体。由于抗生素耐药性增加，需要从天然来源开发更有效的抗菌剂。在本研究中，我们针对两株产金属β-内酰胺酶（MBL）的菌株，靶向这些细菌的群体感应机制（QS）以对抗抗生素耐药性。我们的研究旨在使用几个世纪以来一直在草药中使用的植物化学物质。我们使用了15种市售植物化学物质，并检测它们对生物膜形成、群体感应及相关机制的影响。异甘草素的亚抑菌浓度在第6天抑制P8中生物膜形成55%，在第6天抑制P6中生物膜形成48%；抑制P6中群体感应83%，抑制P8中群体感应61%，而6-姜酚的亚抑菌浓度在第6天抑制P8中生物膜形成48%，在第6天抑制P6中生物膜形成44%；分别抑制P6中群体感应69%，抑制P8中群体感应48%。结果表明，异甘草素、表没食子儿茶素没食子酸酯、丁香酚、木犀草素和白杨素是抑制群体感应及相关机制的潜在候选物。异甘草素从未用于生物膜和群体感应相关研究，显示出显著效果，并且发现其在抑制群体感应方面比已知的群体感应抑制剂6-姜酚更有效。为了研究植物化学物质与群体感应之间的分子相互作用，在植物配体与四种群体感应蛋白之间进行了计算机模拟分子对接。对接分析显示，异甘草素与存在于RhlI活性位点的氨基酸（Trp34、Asp35、Asp35、Tyr105、Arg104、Val138、Thr140）形成强键，结合能值为-8.4 kcal/mol，而6-姜酚与Rhl1的结合能值为-7.3 kcal/mol。总之，我们的研究可能有助于通过利用这些植物化学物质破坏生物膜和抑制群体感应来控制由耐碳青霉烯金属β-内酰胺酶（MBL-PA）引起的医院感染。此外，它们与抗生素的协同作用可能有助于降低碳青霉烯类抗生素对这类多重耐药菌株的最低抑菌浓度。
