van Tilburg Bernardes Erik, Charron-Mazenod Laetitia, Reading David J, Reckseidler-Zenteno Shauna L, Lewenza Shawn
Faculty of Medicine, Department of Microbiology & Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
Snyder Institute of Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.01997-16. Print 2017 May.
Biofilm formation is a universal virulence strategy in which bacteria grow in dense microbial communities enmeshed within a polymeric extracellular matrix that protects them from antibiotic exposure and the immune system. is an archetypal biofilm-forming organism that utilizes a biofilm growth strategy to cause chronic lung infections in cystic fibrosis (CF) patients. The extracellular matrix of biofilms is comprised mainly of exopolysaccharides (EPS) and DNA. Both mucoid and nonmucoid isolates of produce the Pel and Psl EPS, each of which have important roles in antibiotic resistance, biofilm formation, and immune evasion. Given the central importance of the EPS for biofilms, they are attractive targets for novel anti-infective compounds. In this study, we used a high-throughput gene expression screen to identify compounds that repress expression of the genes. The repressors demonstrated antibiofilm activity against microplate and flow chamber biofilms formed by wild-type and hyperbiofilm-forming strains. To determine the potential role of EPS in virulence, / mutants were shown to have reduced virulence in feeding behavior and slow killing virulence assays in The antibiofilm molecules also reduced PAO1 virulence in the nematode slow killing model. Importantly, the combination of antibiotics and antibiofilm compounds increased killing of biofilms. These small molecules represent a novel anti-infective strategy for the possible treatment of chronic infections.
生物膜形成是一种普遍的致病策略，在此过程中细菌在密集的微生物群落中生长，这些群落被包裹在一种聚合的细胞外基质中，该基质可保护它们免受抗生素和免疫系统的影响。[具体细菌名称]是一种典型的生物膜形成生物体，它利用生物膜生长策略在囊性纤维化（CF）患者中引发慢性肺部感染。[具体细菌名称]生物膜的细胞外基质主要由胞外多糖（EPS）和DNA组成。[具体细菌名称]的黏液型和非黏液型分离株均产生Pel和Psl EPS，它们在抗生素抗性、生物膜形成和免疫逃避中均发挥重要作用。鉴于EPS对生物膜至关重要，它们是新型抗感染化合物的有吸引力的靶点。在本研究中，我们使用高通量基因表达筛选来鉴定抑制[具体细菌名称]基因表达的化合物。这些[具体细菌名称]阻遏物对由野生型和超生物膜形成菌株形成的微孔板和流动腔生物膜具有抗生物膜活性。为了确定EPS在致病中的潜在作用，[具体细菌名称]突变体在摄食行为和缓慢致死毒力试验中显示出毒力降低。这些抗生物膜分子在秀丽隐杆线虫缓慢致死模型中也降低了[具体细菌名称]PAO1的毒力。重要的是，抗生素和抗生物膜化合物的组合增强了对[具体细菌名称]生物膜的杀灭作用。这些小分子代表了一种可能用于治疗慢性[具体细菌名称]感染的新型抗感染策略。
