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

View ORCID ProfileIsabel Johnston, View ORCID ProfileLucas J Osborn, View ORCID ProfileRachel L Markley, View ORCID ProfileElizabeth A McManus, View ORCID ProfileAnagha Kadam, View ORCID ProfileKarlee B Schultz, View ORCID ProfileNagashreyaa Nagajothi, View ORCID ProfilePhilip P Ahern, View ORCID ProfileJ Mark Brown, View ORCID ProfileJan Claesen
doi: https://doi.org/10.1101/2020.04.22.055939
Isabel Johnston
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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Lucas J Osborn
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
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Rachel L Markley
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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Elizabeth A McManus
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
3National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
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Anagha Kadam
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
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Karlee B Schultz
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
4College of Arts and Sciences, John Carroll University, University Heights, OH, USA
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Nagashreyaa Nagajothi
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
5University Honors College, University of Pittsburgh, Pittsburgh, PA, USA
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Philip P Ahern
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
6Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
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J Mark Brown
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
6Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
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Jan Claesen
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
2Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA
6Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, OH, USA
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  • For correspondence: claesej@ccf.org
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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.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 11, 2021.
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Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation
Isabel Johnston, Lucas J Osborn, Rachel L Markley, Elizabeth A McManus, Anagha Kadam, Karlee B Schultz, Nagashreyaa Nagajothi, Philip P Ahern, J Mark Brown, Jan Claesen
bioRxiv 2020.04.22.055939; doi: https://doi.org/10.1101/2020.04.22.055939
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Identification of essential genes for Escherichia coli aryl polyene biosynthesis and function in biofilm formation
Isabel Johnston, Lucas J Osborn, Rachel L Markley, Elizabeth A McManus, Anagha Kadam, Karlee B Schultz, Nagashreyaa Nagajothi, Philip P Ahern, J Mark Brown, Jan Claesen
bioRxiv 2020.04.22.055939; doi: https://doi.org/10.1101/2020.04.22.055939

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