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Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation
npj Biofilms and Microbiomes ( IF 9.2 ) Pub Date : 2021-07-02 , DOI: 10.1038/s41522-021-00226-3
Isabel Johnston 1, 2 , Lucas J Osborn 1, 3 , Rachel L Markley 1 , Elizabeth A McManus 1, 4 , Anagha Kadam 1 , Karlee B Schultz 1, 5 , Nagashreyaa Nagajothi 1, 6 , Philip P Ahern 1, 3, 7 , J Mark Brown 1, 3, 7 , Jan Claesen 1, 3, 7
Affiliation  

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.



中文翻译:

大肠杆菌芳基多烯生物合成必需基因的鉴定及其在生物膜形成中的功能

芳基多烯 (APE) 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 (BGC) 家族的产物。它们存在于几种革兰氏阴性宿主相关细菌中,包括耐多药的人类病原体。在这里,我们表征了 APE 的生物学功能,重点是来自尿路致病性大肠杆菌的 BGC(UPEC) 应变。我们首先进行基因缺失分析,以确定 APE 生物合成所需的必需基因。接下来,我们展示了 APE 作为健身因子,可以增加对氧化应激的保护并有助于生物膜形成。总之,我们的研究突出了 APE 生物合成途径中的关键步骤,这些步骤可以作为补充策略的潜在药物靶点进行探索,以降低适应度和防止多重耐药病原体的生物膜形成。

更新日期:2021-07-02
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