Projects per year
Abstract
A wide variety of antibiotics are targeted to the bacterial membrane due to its unique arrangement and composition relative to the host mammalian membranes. By modification of their membranes, some gram-negative pathogens resist the action of antibiotics. Lipid A phosphoethanolamine transferase (EptA) is an intramembrane enzyme that modifies the lipid A portion of lipopolysaccharide/lipooligosaccharide by the addition of phosphoethanolamine. This modification reduces the overall net-negative charge of the outer membrane of some gram-negative bacteria, conferring resistance to polymyxin. This resistance mechanism has resulted in a global public health issue due to the increased use of polymyxin as last-resort antibiotic treatments against multi-drug-resistant pathogens. Studies show that, without EptA, pathogenic bacteria become more sensitive to polymyxin and to clearance by the host immune system, suggesting the importance of this target enzyme for the development of novel therapeutic agents. In this review, EptA will be discussed comprehensively. Specifically, this review will cover the regulation of eptA expression by the two component systems PmrA/PmrB and PhoP/PhoQ, the site of modification on lipid A, the structure and catalytic mechanism of EptA in comparison to MCR-1 and Escherichia coli alkaline phosphatase, and the host immune system's response to lipid A modification by EptA. The overarching aim of this review is to provide a comprehensive overview of polymyxin resistance mediated by EptA.
Original language | English |
---|---|
Pages (from-to) | 5184-5196 |
Number of pages | 13 |
Journal | Journal of Molecular Biology |
Volume | 432 |
Issue number | 18 |
Early online date | 21 Aug 2020 |
DOIs | |
Publication status | Published - 21 Aug 2020 |
Fingerprint
Dive into the research topics of 'Lipid A Phosphoethanolamine Transferase: Regulation, Structure and Immune Response'. Together they form a unique fingerprint.Projects
- 2 Finished
-
Structure-based design of novel therapeutics for multi-drug resistant Neisseria gonorrhoeae
Vrielink, A., Stubbs, K., Scanlon, M. & Kahler, C.
National Health & Medical Research Council NHMRC
1/01/15 → 31/12/19
Project: Research
-
The Role of Lipooligosaccharide Phosphoethanolamine Transferases in the Pathogenesis of Neisseria Meningitidis & N Gonorrhoeae
Kahler, C., Vrielink, A., Scanlon, M. & Carlson, R.
National Health & Medical Research Council NHMRC
1/01/11 → 30/10/14
Project: Research