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

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

来源:bioRxiv_logobioRxiv
英文摘要

ABSTRACT 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 multi-drug 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.

Claesen Jan、Johnston Isabel、McManus Elizabeth A、Nagajothi Nagashreyaa、Kadam Anagha、Ahern Philip P、Markley Rachel L、Schultz Karlee B、Osborn Lucas J、Brown J Mark

Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic||Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University||Center for Microbiome and Human Health, Cleveland ClinicDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland ClinicDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic||National Cancer Institute, National Institutes of HealthDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic||University Honors College, University of PittsburghDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland ClinicDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic||Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University||Center for Microbiome and Human Health, Cleveland ClinicDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland ClinicDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic||College of Arts and Sciences, John Carroll University, University HeightsDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic||Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve UniversityDepartment of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic||Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University||Center for Microbiome and Human Health, Cleveland Clinic

10.1101/2020.04.22.055939

微生物学分子生物学生物化学

Claesen Jan,Johnston Isabel,McManus Elizabeth A,Nagajothi Nagashreyaa,Kadam Anagha,Ahern Philip P,Markley Rachel L,Schultz Karlee B,Osborn Lucas J,Brown J Mark.Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation[EB/OL].(2025-03-28)[2025-06-03].https://www.biorxiv.org/content/10.1101/2020.04.22.055939.点此复制

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