Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation.
Isabel JohnstonLucas J OsbornRachel L MarkleyElizabeth A McManusAnagha KadamKarlee B SchultzNagashreyaa NagajothiPhilip P AhernJ Mark BrownJan ClaesenPublished in: NPJ biofilms and microbiomes (2021)
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.
Keyphrases
- biofilm formation
- multidrug resistant
- gram negative
- drug resistant
- escherichia coli
- pseudomonas aeruginosa
- staphylococcus aureus
- acinetobacter baumannii
- candida albicans
- genome wide
- klebsiella pneumoniae
- oxidative stress
- physical activity
- body composition
- copy number
- genome wide identification
- bioinformatics analysis
- endothelial cells
- cell wall
- fatty acid
- palliative care
- molecular docking
- emergency department
- gene expression
- antimicrobial resistance
- induced apoptosis