Quorum Sensing Signal Molecule Modulation Of Immunity: Role In Host Responses To P. Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$251,014.00
Summary
Pseudomonas aeruginosa is a bacterium that causes serious infections in humans, particularly those with Cystic Fibrosis, or who are immunocompromised, suffering serious burn injuries or have long term catheters. This study will investigate how P. aeruginosa may be able to increase its virulence by producing molecules known as Quorum Sensing Signal Molecules (QSSM). We believe the production of these QSSMs by this bacterium enables them to affect how the host responds by affecting their immune sy ....Pseudomonas aeruginosa is a bacterium that causes serious infections in humans, particularly those with Cystic Fibrosis, or who are immunocompromised, suffering serious burn injuries or have long term catheters. This study will investigate how P. aeruginosa may be able to increase its virulence by producing molecules known as Quorum Sensing Signal Molecules (QSSM). We believe the production of these QSSMs by this bacterium enables them to affect how the host responds by affecting their immune system. We will be investigating how this QSSM may suppress immunity and what influence this has on both the severity of infection and the potential for development of chronic infection. The study will first of all determine where the QSSM exerts its effects (that is, can it escape from the site of infection to affect other host sites) and this will direct us in how we may learn more about the way it can affect the host during an infection. We will investigate the direct affects of QSSM on acute and chronic types of P. aeruginosa lung infection and then from this, determine if the outcome exacerbates a subsequent infection. The work is significant in that a knowledge and understanding of these virulence factors will assist in the design of better therapeutic and prophylactic strategies for both prevention of infection in susceptible individuals and treatment of those that suffer from chronic infection.Read moreRead less
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
A Novel Strategy Targeting Quorum Sensing Molecules And Catalase Function To Block Pseudomonas Aeruginosa Lung Infection
Funder
National Health and Medical Research Council
Funding Amount
$451,118.00
Summary
Pseudomonas aeruginosa causes serious infections, particularly in those with Cystic Fibrosis, immunocompromise, serious burns or long term catheters. We will use a unique strategy to target virulence factors that will assist in clearing acute infection, prevent establishment of new chronic infections, and potentially reduce severity of established chronic infections. It has the potential to make antibiotic therapy more effective and lessen the extent of antibiotic therapy required.
Mechanism Of Exacerbations In Cystic Fibrosis Lung Disease
Funder
National Health and Medical Research Council
Funding Amount
$254,876.00
Summary
Cystic Fibrosis lung disease is characterised by infeciton with a bug called Pseudomonas aeruginosa. Patients ultimately die in their mid-30's as a result of this infection, but lung decline is accelerated by episodes of exacerbation when patients cough up large volumes of mucky sputum. We are studying the casue of exacerbations by looking at bacterial behaviour and the response of the immune system. We will use this information to try and develop early warning signals and better treatments.
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.