Phosphoethanolamine cellulose : discovery, biosynthesis, and importance in e. coli biofilms

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Abstract/Contents

Abstract
Biofilms are multicellular communities of cells embedded in a self-secreted extracellular matrix (ECM), a complex polymeric mixture that protects cells from harsh environments including antibiotic treatments. Our solid-state NMR analysis of the ECM material produced by uropathogenic E. coli, the most common causative agent of urinary tract infections, led to an unanticipated discovery that E. coli naturally produces a modified form of cellulose— phosphoethanolamine (pEtN) cellulose. Cellulose is the most abundant biopolymer on Earth and this discovery provided the first example of a chemically modified cellulose in nature. We investigated the biosynthesis of pEtN cellulose and determined the unknown functions of bcsEFG genes to be involved in the modification of cellulose. BcsG was identified as the necessary phosphoethanolamine transferase that installs the pEtN functionality on the cellulose via a BcsE-BcsF-BcsG transmembrane signaling pathway. To facilitate further investigation of pEtN cellulose, we developed new approaches to identify and study pEtN cellulose. These include: (1) a Congo red fluorescence method to distinguish pEtN cellulose from unmodified cellulose, (2) the 15N-serine biosynthetic labelling strategy to incorporate 15N into pEtN cellulose, and (3) the use of Closantel to suppress curli production in biofilms and enable facile detection of the cellulosic material. We employed each of these new approaches to evaluate uropathogenic E. coli clinical isolates for their abilities to produce pEtN cellulose. Our findings demonstrate the importance of the pEtN modification of cellulose in E. coli biofilm formation. They will be of value in ongoing studies of new strains and conditions that might affect pEtN cellulose production in bacteria. Our study of pEtN cellulose has implications for developing novel materials biosynthetically and alternative strategies to treat bacterial infections. Since the pEtN modification of cellulose contributes to biofilm formation, it provides a promising therapeutic target for anti-infective treatments to avoid the use of traditional antibiotics which can lead to antibiotic resistance.

Description

Type of resource text
Form electronic resource; remote; computer; online resource
Extent 1 online resource.
Place California
Place [Stanford, California]
Publisher [Stanford University]
Copyright date 2019; ©2019
Publication date 2019; 2019
Issuance monographic
Language English

Creators/Contributors

Author Thongsomboon, Wiriya
Degree supervisor Cegelski, Lynette
Thesis advisor Cegelski, Lynette
Thesis advisor Cui, Bianxiao
Thesis advisor Kool, Eric T
Degree committee member Cui, Bianxiao
Degree committee member Kool, Eric T
Associated with Stanford University, Department of Chemistry.

Subjects

Genre Theses
Genre Text

Bibliographic information

Statement of responsibility Wiriya Thongsomboon.
Note Submitted to the Department of Chemistry.
Thesis Thesis Ph.D. Stanford University 2019.
Location electronic resource

Access conditions

Copyright
© 2019 by Wiriya Thongsomboon
License
This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).

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