The role of lipid A in the virulence of ESKAPE pathogens
type: CreativeWork
description: The exponential growth of antimicrobial resistance worldwide is one of the most concerning threats to mankind in the modern era. Gram-negative bacterial infections are of particular concern and have been identified as an urgent threat by governmental organisations. The Gram-negative pathogens Acinetobacter baumannii and Klebsiella pneumoniae have been highlighted as critical priority pathogens for research and development of novel therapeutics. Both of these pathogens share notoriety for their readiness to develop resistance to all antibiotics currently in circulation, including those of last resort. Antimicrobial resistance increases mortality and morbidity in addition to increasing the rate of diseases such as sepsis due to limited treatment options. Therefore, life-threatening conditions such as septic shock can be sequalae to previously unthreatening diseases such as urinary tract infections and small wounds. Bloodstream infections are a leading cause of mortality in critically ill patients, of which Gram-negative bacteraemia accounts for a large proportion of all hospitalised cases. Lipopolysaccharide/lipooligosaccharide (LPS/LOS) present on the outer membrane of Gram-negative pathogens is the main sepsis-inducing agent known for its significant inflammatory capabilities during septic shock. Here we investigated the lipid A anchoring moiety of A. baumannii LOS which is the most pronounced pro-inflammatory molecule of A. baumannii. Several studies have elucidated A. baumannii lipid A modifications and their role in virulence. Therefore, we investigated the role of the previously unidentified lipid A-remodelling enzyme in A. baumannii and explored its contribution to virulence and resistance to last-resort antibiotics. These findings have identified a novel target for the development of new, urgent antimicrobial compounds. In agreement with published literature, our results may allow development of a broad-spectrum compound against other Gram-negative pathogens p…
abstract: The exponential growth of antimicrobial resistance worldwide is one of the most concerning threats to mankind in the modern era. Gram-negative bacterial infections are of particular concern and have been identified as an urgent threat by governmental organisations. The Gram-negative pathogens Acinetobacter baumannii and Klebsiella pneumoniae have been highlighted as critical priority pathogens for research and development of novel therapeutics. Both of these pathogens share notoriety for their readiness to develop resistance to all antibiotics currently in circulation, including those of last resort. Antimicrobial resistance increases mortality and morbidity in addition to increasing the rate of diseases such as sepsis due to limited treatment options. Therefore, life-threatening conditions such as septic shock can be sequalae to previously unthreatening diseases such as urinary tract infections and small wounds. Bloodstream infections are a leading cause of mortality in critically ill patients, of which Gram-negative bacteraemia accounts for a large proportion of all hospitalised cases. Lipopolysaccharide/lipooligosaccharide (LPS/LOS) present on the outer membrane of Gram-negative pathogens is the main sepsis-inducing agent known for its significant inflammatory capabilities during septic shock. Here we investigated the lipid A anchoring moiety of A. baumannii LOS which is the most pronounced pro-inflammatory molecule of A. baumannii. Several studies have elucidated A. baumannii lipid A modifications and their role in virulence. Therefore, we investigated the role of the previously unidentified lipid A-remodelling enzyme in A. baumannii and explored its contribution to virulence and resistance to last-resort antibiotics. These findings have identified a novel target for the development of new, urgent antimicrobial compounds. In agreement with published literature, our results may allow development of a broad-spectrum compound against other Gram-negative pathogens p…
author: Bartholomew, Toby
language: eng
date published: 2019
date modified: 2026-07-24T03:54:59Z
provider: Queen's University Belfast
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Queen's University Belfast