Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Institut de Biologie Intégrative et des Systèmes (IBIS), Pavillon Charles-Eugène-Marchand, Université Laval, Quebec City, QC, G1V 0A6, Canada.
BMC Microbiol. 2023 Jan 19;23(1):23. doi: 10.1186/s12866-023-02758-4.
The emergence of multidrug-resistant Acinetobacter baumannii strains is increasing worldwide. To overcome these life-threatening infections, the development of new treatment approaches is critical. For this purpose, this study was conducted to determine the antimicrobial photo-sonodynamic therapy (aPSDT) using hypericin nanoparticles (HypNP) in combination with D-Tryptophan (D-Trp) against A. baumannii.
HypNP was synthesized and characterized, followed by the determination of the fractional inhibitory concentration (FIC) index of HypNP and D-Trp by checkerboard assay. Next, the antimicrobial and anti-biofilm potential of HypNP@D-Trp-mediated aPSDT against A. baumannii was evaluated. Finally, the anti-virulence activity of aPSDT using HypNP@D-Trp was accessed following the characterization of HypNP@D-Trp interaction with AbaI using in silico virtual screening and molecular docking.
A synergistic activity in the combination of HypNP and D-Trp against A. baumannii was observed with a FIC index value of 0.5. There was a 5.10 log CFU/mL reduction in the cell viability of A. baumannii when the bacterial cells were treated with 1/2 × MIC of HypNP@D-Trp and subsequently exposed to ultrasound waves and blue light (P < 0.05). Moreover, a significant biofilm degradation effect on biofilm-associated cells of A. baumannii was observed after treatment with aPSDT using 2 × MIC of HypNP@D-Trp in comparison with the control groups (P < 0.05). According to the molecular docking analysis of the protein-ligand complex, Hyp with a high affinity for AbaI showed a binding affinity of - 9.41 kcal/mol. Also, the expression level of abaI gene was significantly downregulated by 10.32-fold in A. baumannii treated with aPSDT as comprised with the control group (P < 0.05).
It can be concluded that HypNP@D-Trp-mediated aPSDT can be considered a promising strategy to overcome the infections caused by A. baumannii by reducing the growth of bacterial biofilm and decreasing the expression of abaI as a gene involved in A. baumannii biofilm formation.
多药耐药鲍曼不动杆菌菌株的出现正在全球范围内增加。为了克服这些危及生命的感染，开发新的治疗方法至关重要。为此，本研究旨在确定使用金丝桃素纳米粒子（HypNP）与 D-色氨酸（D-Trp）联合进行的光动力抗菌治疗（aPSDT）对鲍曼不动杆菌的作用。
合成并表征 HypNP，然后通过棋盘试验确定 HypNP 和 D-Trp 的部分抑制浓度（FIC）指数。接下来，评估 HypNP@D-Trp 介导的 aPSDT 对鲍曼不动杆菌的抗菌和抗生物膜潜力。最后，通过 HypNP@D-Trp 与 AbaI 的相互作用的计算机虚拟筛选和分子对接来评估使用 HypNP@D-Trp 的抗毒力活性。
观察到 HypNP 和 D-Trp 联合使用对鲍曼不动杆菌具有协同作用，FIC 指数值为 0.5。当细菌细胞用 1/2×MIC 的 HypNP@D-Trp 处理，然后暴露于超声波和蓝光下时，鲍曼不动杆菌的细胞活力降低了 5.10 对数 CFU/mL（P<0.05）。此外，与对照组相比，用 HypNP@D-Trp 的 2×MIC 处理后，观察到鲍曼不动杆菌生物膜相关细胞的生物膜降解效果显著（P<0.05）。根据蛋白质-配体复合物的分子对接分析，Hyp 与 AbaI 具有高亲和力，表现出 -9.41 kcal/mol 的结合亲和力。此外，与对照组相比，经 aPSDT 处理的鲍曼不动杆菌中 abaI 基因的表达水平显著下调了 10.32 倍（P<0.05）。
可以得出结论，HypNP@D-Trp 介导的 aPSDT 可以被认为是一种有前途的策略，可以通过减少细菌生物膜的生长和降低参与鲍曼不动杆菌生物膜形成的 abaI 基因的表达来克服由鲍曼不动杆菌引起的感染。
