Project Details
Description
Bacterial pneumonia and sepsis are primary causes of morbidity and mortality in critically ill ICU patients, a challenge that is further complicated by the global rise in antibiotic resistance. The bacterial membrane represents a critical barrier against antimicrobial stress and is therefore an appealing target for enhancing antibiotic efficacy and immune-mediated clearance. However, a poor understanding of lipid homeostasis in bacteria at the host-pathogen interface limits our ability to exploit this strategy.
Bacteria prefer acquiring lipids from their environment compared to the synthesis of these energy-rich biomolecules. Yet, some host lipids, such as those with polyunsaturated fatty acid tails, can have deleterious impacts on bacterial virulence and antibiotic resistance. From a host perspective, hyperlipidaemia, a core pathology of obesity, is correlated with an increased risk of developing bacterial infections. Paradoxically, elevated lipid levels can lower morality rates during severe pneumonia and sepsis. Collectively, these factors demonstrate that both the host and pathogen require delicate regulation of lipid homeostasis during infection.
This project aims to characterise the full repertoire of lipid homeostasis mechanisms in Acinetobacter baumannii, which is recognised by the CDC and WHO as a critical hospital pathogen. We will use molecular, biochemical and computational analyses to interrogate changes in the A. baumannii membrane composition and biophysical properties, when isolated from different infection sites in mice, each with unique lipid landscapes. We will also explore dietary and pharmaceutical lipid modulation strategies to reduce A. baumannii pathogenesis in infection susceptible obese hosts.
The project outcomes will yield novel insights into the central role of lipids at the host-pathogen interface, to ultimately provide healthcare practitioners with additional intervention strategies when fighting live-threatening hospital infections.
Bacteria prefer acquiring lipids from their environment compared to the synthesis of these energy-rich biomolecules. Yet, some host lipids, such as those with polyunsaturated fatty acid tails, can have deleterious impacts on bacterial virulence and antibiotic resistance. From a host perspective, hyperlipidaemia, a core pathology of obesity, is correlated with an increased risk of developing bacterial infections. Paradoxically, elevated lipid levels can lower morality rates during severe pneumonia and sepsis. Collectively, these factors demonstrate that both the host and pathogen require delicate regulation of lipid homeostasis during infection.
This project aims to characterise the full repertoire of lipid homeostasis mechanisms in Acinetobacter baumannii, which is recognised by the CDC and WHO as a critical hospital pathogen. We will use molecular, biochemical and computational analyses to interrogate changes in the A. baumannii membrane composition and biophysical properties, when isolated from different infection sites in mice, each with unique lipid landscapes. We will also explore dietary and pharmaceutical lipid modulation strategies to reduce A. baumannii pathogenesis in infection susceptible obese hosts.
The project outcomes will yield novel insights into the central role of lipids at the host-pathogen interface, to ultimately provide healthcare practitioners with additional intervention strategies when fighting live-threatening hospital infections.
| Acronym | ID24 (Flinders led) |
|---|---|
| Status | Active |
| Effective start/end date | 1/01/25 → 31/12/27 |