Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Inflammation & Immunity, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA.
NPJ Biofilms Microbiomes. 2021 Jul 2;7(1):56. doi: 10.1038/s41522-021-00226-3.
Aryl polyenes (APEs) are specialized polyunsaturated carboxylic acids that were identified in silico as the product of the most widespread family of bacterial biosynthetic gene clusters (BGCs). They are present in several Gram-negative host-associated bacteria, including multidrug-resistant human pathogens. Here, we characterize a biological function of APEs, focusing on the BGC from a uropathogenic Escherichia coli (UPEC) strain. We first perform a genetic deletion analysis to identify the essential genes required for APE biosynthesis. Next, we show that APEs function as fitness factors that increase protection from oxidative stress and contribute to biofilm formation. Together, our study highlights key steps in the APE biosynthesis pathway that can be explored as potential drug targets for complementary strategies to reduce fitness and prevent biofilm formation of multi-drug resistant pathogens.
芳基多烯(APEs)是一种特殊的多不饱和羧酸,在计算机中被鉴定为最广泛的细菌生物合成基因簇(BGCs)家族的产物。它们存在于几种革兰氏阴性宿主相关细菌中,包括多药耐药的人类病原体。在这里,我们研究了 APEs 的生物学功能,重点是来自尿路致病性大肠杆菌(UPEC)菌株的 BGC。我们首先进行了遗传缺失分析,以确定 APE 生物合成所需的必需基因。接下来,我们表明 APEs 作为适应因子发挥作用,增加了对氧化应激的保护,并有助于生物膜的形成。总之,我们的研究强调了 APE 生物合成途径中的关键步骤,可以作为潜在的药物靶点,探索减少多药耐药病原体适应性和防止生物膜形成的互补策略。