Abstract：
Bacterial pigments represent a diverse group of secondary metabolites, which confer fitness advantages to the producers while residing in communities. The bioactive potential of such metabolites, including antimicrobial, anticancer, and immunomodulation, are being explored. Reckoning that a majority of such pigments are produced in response to quorum sensing (QS) mediated expression of biosynthetic gene clusters and, in turn, influence cell-cell communication, systemic profiling of the pigments for possible impact on QS appears crucial. A systemic screening of bacterial pigments for QS-inhibition combined with exploration of antibiofilm and antimicrobial action against Acinetobacter baumannii might offer viable alternatives to combat the priority pathogen. Major bacterial pigments are classified (clustered) based on their physicochemical properties, and representatives of the clusters are screened for QS inhibition. The screen highlighted prodigiosin as a potent quorum quencher, although its production from Serratia marcescens appeared to be QS-independent. In silico analysis indicated potential interactions between AbaI and AbaR, two major QS regulators in A. baumannii, and prodigiosin, which impaired biofilm formation, a major QS-dependent process in the bacteria. Prodigiosin augmented antibiotic action of ciprofloxacin against A. baumannii biofilms. Cell viability analysis revealed prodigiosin to be modestly cytotoxic against HEK293, a non-cancer human cell line. While developing dual-species biofilm, prodigiosin producer S. marcescens significantly impaired the fitness of A. baumannii. Enhanced susceptibility of A. baumannii toward colistin was also noted while growing in co-culture with S. marcescens. Antibiotic resistant isolates demonstrated varied responsiveness against prodigiosin, with two resistant strains demonstrating possible collateral sensitivity. Collectively, the results underpin the prospect of a prodigiosin-based therapeutic strategy in combating A. baumannii infection.
摘要：
细菌色素代表了一组不同的次级代谢产物，这赋予生产者在社区居住时的健身优势。这些代谢物的生物活性潜力，包括抗菌药物,抗癌，和免疫调节，正在探索。估计大多数此类色素是响应于生物合成基因簇的群体感应（QS）介导的表达而产生的，反过来,影响细胞间的通讯，对可能影响QS的颜料进行系统分析似乎至关重要。对细菌色素进行系统的QS抑制筛选，并探索抗生物膜和对鲍曼不动杆菌的抗菌作用，可能为对抗优先病原体提供可行的替代方案。主要的细菌色素根据其物理化学性质进行分类（成簇），并对簇的代表进行QS抑制筛选。屏幕上突出显示prodigiosin是一种有效的群体猝灭剂，尽管其生产的粘质沙雷氏菌似乎与QS无关。计算机模拟分析表明AbaI和AbaR之间存在潜在的相互作用，鲍曼不动杆菌的两个主要QS监管机构，和prodigiosin，这损害了生物膜的形成，细菌中主要的QS依赖性过程。Prodigiosin增强环丙沙星对鲍曼不动杆菌生物膜的抗生素作用。细胞活力分析显示，prodigiosin对非癌症人类细胞系HEK293具有适度的细胞毒性。在开发双物种生物膜的同时，prodigiosin生产者S.marcescens显着损害鲍曼不动杆菌的适应性。鲍曼不动杆菌与粘质链球菌共培养时对粘菌素的敏感性也增加。抗生素抗性分离株对prodigiosin表现出不同的反应性，两个耐药菌株显示可能的侧支敏感性。总的来说，该结果支持了基于prodigiosin的治疗策略在对抗鲍曼不动杆菌感染中的前景。
