Anti-infective synergy of Acacia nilotica bioactive fraction and methyl gallate with meropenem against pathogenicity of Pseudomonas aeruginosa.

IF 2.9 4区生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

3 Biotech Pub Date : 2025-07-01 Epub Date: 2025-06-11 DOI:10.1007/s13205-025-04372-9

Samreen, Iqbal Ahmad

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Abstract

A combination approach using phytocompounds with antibiotics offers a promising strategy to enhance antibiotic efficacy and reduce pathogen virulence. This study investigates the synergistic antibacterial and anti-virulence potential of Acacia nilotica ethyl acetate fraction (ANEF) and its bioactive compound, methyl gallate (MG), in combination with meropenem against Pseudomonas aeruginosa PAO1. The synergy was assessed using checkerboard assays against P. aeruginosa and Escherichia coli, with ANEF-meropenem and MG-meropenem combinations yielding fractional inhibitory concentration index (FICI) values of 0.187 and 0.312, respectively, indicating strong synergism. These combinations significantly reduced bacterial viability, with log₁₀ CFU/ml reductions of 4.48 (ANEF-meropenem) and 3.68 (MG-meropenem). The combinations inhibited quorum sensing (QS)-regulated virulence factors, including pyocyanin, pyoverdine, protease, swarming, and EPS production by 58-82% at ½ FIC. The biofilm disruption assays further confirmed the anti-biofilm potential, with reductions of 86.67% by ANEF-meropenem and 82.66% for the MG-meropenem combination. The mechanistic evaluations revealed enhanced bacterial membrane disruption, with MG-meropenem showing the highest membrane permeability (54.63% dye uptake) and cellular leakage (OD 1.28). Hemolysis assays indicated dose-dependent toxicity, with maximum hemolysis by 45.39% (ANEF) and 29.94% (MG) at the MIC value. However, ANEF exhibited no adverse developmental effects in Caenorhabditis elegans N2 worms. These findings demonstrate that ANEF and MG, in synergy with meropenem, effectively impair P. aeruginosa growth, virulence, and biofilm formation while maintaining low toxicity profiles. The findings support the potential of phytochemical-antibiotic combinations as promising adjunct therapies for multidrug-resistant P. aeruginosa infections.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-025-04372-9.

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相思生物活性部位和没食子酸甲酯与美罗培南协同抗铜绿假单胞菌致病性的研究。

将植物化合物与抗生素结合使用为提高抗生素疗效和降低病原体毒力提供了一种很有前途的策略。本研究探讨了尼罗卡槐乙酸乙酯部位（ANEF）及其活性化合物没食子酸甲酯（MG）与美罗培南联合对铜绿假单胞菌PAO1的协同抑菌和抗毒作用。采用棋盘法对铜绿假单胞菌和大肠埃希菌进行了协同作用评价，anef -美罗培南和mg -美罗培南联合用药的分数抑制浓度指数（FICI）分别为0.187和0.312，显示了较强的协同作用。这些组合显著降低了细菌活力，对数0 CFU/ml降低4.48 （anef -美罗培南）和3.68 （mg -美罗培南）。在1 / 2 FIC下，这些组合抑制了群体感应（QS）调节的毒力因子，包括pyocyanin， pyoverdine，蛋白酶，蜂群和EPS的产生58-82%。生物膜破坏实验进一步证实了抗生物膜的潜力，anef -美罗培南和mg -美罗培南联合的抗生物膜效果分别为86.67%和82.66%。机制评价显示细菌膜破坏增强，mg -美罗培南显示最高的膜通透性（54.63%的染料摄取）和细胞渗漏（OD为1.28）。溶血试验显示剂量依赖性毒性，在MIC值下最大溶血率为45.39% （ANEF）和29.94% （MG）。然而，ANEF对秀丽隐杆线虫的发育没有不良影响。这些发现表明，ANEF和MG与美罗培南协同作用，有效地抑制铜绿假单胞菌的生长、毒力和生物膜的形成，同时保持低毒性。这些发现支持植物化学-抗生素联合治疗作为耐多药铜绿假单胞菌感染的有希望的辅助疗法的潜力。补充信息：在线版本包含补充资料，下载地址：10.1007/s13205-025-04372-9。

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来源期刊

3 Biotech Agricultural and Biological Sciences-Agricultural and Biological Sciences (miscellaneous)

CiteScore

6.00

自引率

0.00%

发文量

314

期刊介绍： 3 Biotech publishes the results of the latest research related to the study and application of biotechnology to: - Medicine and Biomedical Sciences - Agriculture - The Environment The focus on these three technology sectors recognizes that complete Biotechnology applications often require a combination of techniques. 3 Biotech not only presents the latest developments in biotechnology but also addresses the problems and benefits of integrating a variety of techniques for a particular application. 3 Biotech will appeal to scientists and engineers in both academia and industry focused on the safe and efficient application of Biotechnology to Medicine, Agriculture and the Environment.