Iron, Pseudomonas Aeruginosa And Lung Disease In Cystic Fibrosis.
Funder
National Health and Medical Research Council
Funding Amount
$322,875.00
Summary
Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to inc ....Cystic fibrosis (CF) is the most common lethal geneticdisease in Caucasians. The worldwide incidence of the disorder is approximately 1 in 2,500 live births. The most significant clinical manifestation of CF is chronic lung infection, particularly with the bacterium, Pseudomonas aeruginosa. Even with the current aggressive antibiotic treatment regimens most patients ultimately succumb to infection with this organism and die before they reach 40 years-of-age. The overall aim of our work is to increase the understanding of how P. aeruginosa persists in the CF lung, with the goal of developing more effective therapeutic strategies to eliminate chronic infection with this bacterium. The new perception is that P. aeruginosa bacteria flourish in mucus with a low oxygen content within the CF lung and persist despite aggressive antibiotic therapy because they have adopted an antibiotic-resistant, biofilm mode of growth. This has opened up exciting directions for new therapeutic strategies. Factors in CF mucus that regulate this mode of bacterial growth are potential targets for intervention. Our past work has shown that iron is likely to be one such factor. In this study, we will extend these findings and determine whether using iron-binding chemicals can disrupt these biofims and allow the host immune system and antibiotics to work more efficiently to kill the bacteria. Not only will this study provide further insights into the pathogenesis of P. aeruginosa in CF and the role of iron, but ultimately it will contribute to the improved treatment and prevention of chronic infection with this organism.Read moreRead less
Analysis Of A Chemosensory Complex That Controls Twitching Motility And Virulence In Pseudomonas Aeruginosa
Funder
National Health and Medical Research Council
Funding Amount
$346,250.00
Summary
Pseudomonas aeruginosa is a common bacterium which causes serious life-threatening infections of individuals with cystic fibrosis, AIDS or who have suffered severe burns or are undergoing cancer chemotherapy. Infection by this pathogen requires the controlled expression of a large number of virulence factors including extracellular enzyme, toxins and structures for the attachment and colonisation of host tissues. We have identified a complex multicomponent regulatory system which coordinates the ....Pseudomonas aeruginosa is a common bacterium which causes serious life-threatening infections of individuals with cystic fibrosis, AIDS or who have suffered severe burns or are undergoing cancer chemotherapy. Infection by this pathogen requires the controlled expression of a large number of virulence factors including extracellular enzyme, toxins and structures for the attachment and colonisation of host tissues. We have identified a complex multicomponent regulatory system which coordinates the expression of many of the virulence determinants of this pathogen. This project aims to dissect the intermolecular interactions and signalling events which input into, occur within, and output from this regulatory system. This knowledge will provide a platform for developing rational strategies for the production of new antimicrobials for fighting infections by this and related pathogens.Read moreRead less
The Effect Of Defective Iron Handling On Immune Function And Pseudomonas Aeruginosa Infection In The Cystic Fibrosis Lung
Funder
National Health and Medical Research Council
Funding Amount
$97,213.00
Summary
In this research higher degree I will study the effects of iron on airway sepsis in cystic fibrosis (CF), with a particular focus on the major pathogen Pseudomonas aeruginosa. Increased concentrations of iron have been described in the CF lung, and CF airway epithelial cells display abnormal iron handling which facilitates P. aeruginosa growth. I will explore imposed iron limitation combined with conventional antibiotics as a new therapeutic strategy for treatment of chronic airway infection.
Identification Of Proteins Specific To Transmissible Pseudomonas Aeruginosa In Cystic Fibrosis Infection
Funder
National Health and Medical Research Council
Funding Amount
$443,007.00
Summary
Cystic fibrosis (CF) is the most common autosomal recessive disorder in humans, affecting 1:2000 people. Mortality is often caused by Pseudomonas aeruginosa lung infections which have recently been shown to occur not only environmentally but also via person-person contact, usually during CF clinic visits. This project will elucidate the molecular traits responsible for these 'epidemic' P. aeruginosa infections, with the aim of finding novel therapeutics and infection control strategies.