Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation

Author:

Johnston IsabelORCID,Osborn Lucas J.ORCID,Markley Rachel L.,McManus Elizabeth A.,Kadam Anagha,Schultz Karlee B.ORCID,Nagajothi Nagashreyaa,Ahern Philip P.ORCID,Brown J. Mark,Claesen JanORCID

Abstract

AbstractAryl 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.

Funder

U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases

Prevent Cancer Foundation

American Cancer Society

Case Comprehensive Cancer Center, Case Western Reserve University

Publisher

Springer Science and Business Media LLC

Subject

Applied Microbiology and Biotechnology,Microbiology,Biotechnology

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