Abstract

Implant-associated infections mediated by Acinetobacter baumannii biofilms have become a major concern in the healthcare sector. As biofilm formation by this important pathogen is mediated by quorum sensing, quorum sensing inhibitors (QSI) have gained much attention. The present study confirms that novel thiazolinyl-picolinamide based palladium(II) complexes had good biofilm disruptive and QSI properties against A. baumannii. Key QS-mediated virulence factors like pili mediated surface motility and polysaccharide production were inhibited by the best Pd(II) complex (E). This also showed potent inhibitory activity against both the standard and clinical strains of A. baumannii. Molecular docking analysis also proved the potent binding affinity of Pd(II)-E with the virulence targets. The Pd(II) complex also disrupted preformed biofilms and down-regulated the expression of QS mediated virulence genes in the biofilms established on implant material (titanium plates). As a whole, the present study showed that the novel thiazolinyl-picolinamide based Pd(II) complexes offer a promising anti-infective strategy to combat biofilm-mediated implant infections.

摘要

鲍曼不动杆菌生物膜介导的种植体相关感染已成为医疗保健领域的主要关注点。由于这种重要病原体的生物膜形成是由群体感应介导的，因此群体感应抑制剂 (QSI) 受到了广泛关注。本研究证实，新型噻唑啉基-吡啶酰胺基钯 (II) 配合物对鲍曼不动杆菌具有良好的生物膜破坏性和 QSI 特性。最好的 Pd(II) 复合物 (E) 抑制了关键的 QS 介导的毒力因子，如菌毛介导的表面运动和多糖的产生。这也显示出对鲍曼不动杆菌的标准菌株和临床菌株的有效抑制活性。分子对接分析也证明了 Pd(II)-E 与毒力目标的有效结合亲和力。Pd(II) 复合物还破坏了预先形成的生物膜，并下调了植入材料（钛板）上建立的生物膜中 QS 介导的毒力基因的表达。总体而言，本研究表明，新型噻唑啉基-吡啶酰胺基 Pd(II) 配合物为对抗生物膜介导的植入物感染提供了一种有前景的抗感染策略。