Acinetobacter baumannii has been reported as a multidrug-resistant bacterium due to biofilms and antimicrobial resistance mechanisms. Hence, novel therapeutic strategies are necessary to overcome A. baumannii infections. This study revealed that citral at 200 μg/ml attenuated A. baumannii biofilms by up to 90% without affecting viability. Furthermore, microscopic analyses and in vitro assays confirmed the antibiofilm efficacy of citral. The global effect of citral on A. baumannii was evaluated by proteomic, transcriptional, and in silico approaches. Two-dimensional (2D) gel electrophoresis and matrix-assisted laser desorption ionization–time of flight/time of flight (MALDI-TOF/TOF) analyses were used to assess the effect of citral on the A. baumannii cellular proteome. Quantitative real-time PCR (qPCR) analysis was done to validate the proteomic data and identify the differentially expressed A. baumannii genes. Protein-protein interactions, gene enrichment, and comparative gene network analyses were performed to explore the interactions and functional attributes of differentially expressed proteins of A. baumannii. Global omics-based analyses revealed that citral targeted various mechanisms such as biofilm formation, antibiotic resistance, antioxidant defense, iron acquisition, and type II and type IV secretion systems. The results of antioxidant analyses and antibiotic sensitivity, blood survival, lipase, and hemolysis assays validated the proteomic results. Cytotoxicity analysis showed a nontoxic effect of citral on peripheral blood mononuclear cells (PBMCs). Overall, the current study unveiled that citral has multitarget efficacy to inhibit the biofilm formation and virulence of A. baumannii.

中文翻译：

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蛋白质组学和系统功能分析揭示了柠檬醛靶向鲍曼不动杆菌的抗生素抗性，抗氧化防御和生物膜相关的两组分系统，从而阻碍了生物膜和毒力的特性

由于生物膜和抗菌素耐药机制，鲍曼不动杆菌已被报告为一种多药耐药细菌。因此，必须有新颖的治疗策略来克服鲍曼不动杆菌的感染。这项研究表明，柠檬醛浓度为200μg/ ml时，鲍曼不动杆菌生物膜最多可衰减90％，而不会影响生存力。此外，显微镜分析和体外测定证实了柠檬醛的抗生物膜功效。柠檬醛对鲍曼不动杆菌的总体作用已通过蛋白质组学，转录和计算机模拟来评估方法。二维（2D）凝胶电泳和基质辅助激光解吸电离–飞行时间/飞行时间（MALDI-TOF / TOF）分析用于评估柠檬醛对鲍曼不动杆菌蛋白质组的影响。进行了实时定量PCR（qPCR）分析，以验证蛋白质组学数据并鉴定差异表达的鲍曼不动杆菌基因。进行蛋白质-蛋白质相互作用，基因富集和比较基因网络分析，以探索鲍曼不动杆菌差异表达蛋白质的相互作用和功能特性。基于全球组学的分析表明，柠檬醛靶向多种机制，例如生物膜形成，抗生素抗性，抗氧化剂防御，铁吸收以及II型和IV型分泌系统。抗氧化剂分析和抗生素敏感性，血液存活率，脂肪酶和溶血分析的结果验证了蛋白质组学结果。细胞毒性分析表明，柠檬醛对外周血单个核细胞（PBMC）无毒。总体而言，当前的研究表明，柠檬醛具有抑制鲍曼不动杆菌生物膜形成和致病性的多靶点功效。