Multi-copper Oxidase Mediated Iron Uptake In Ps. Aeruginosa And Other Pathogenic Bacteria: Mechanism And Role In Disease
Funder
National Health and Medical Research Council
Funding Amount
$73,500.00
Summary
Iron is essential for the growth of bacteria. One of the mechanisms used by humans (and other animals) to defend against bacteria that cause disease is to trap iron by binding it to a set of iron binding proteins eg. transferrin. In this way there is no free iron in the system, so bacteria that survive in humans have had to evolve specific mechanisms to remove the iron form these host proteins. The mechanisms of iron uptake in pathogenic bacteria have been studied extensively, and the iron uptak ....Iron is essential for the growth of bacteria. One of the mechanisms used by humans (and other animals) to defend against bacteria that cause disease is to trap iron by binding it to a set of iron binding proteins eg. transferrin. In this way there is no free iron in the system, so bacteria that survive in humans have had to evolve specific mechanisms to remove the iron form these host proteins. The mechanisms of iron uptake in pathogenic bacteria have been studied extensively, and the iron uptake systems are considered to be important of virulence factors (bacterial factors essential for causing disease). Humans and other higher organisms like Yeast have an iron uptake system that uses multi copper oxidase proteins (MCOs). These proteins have a ferroxidase activity, which converts iron from a protein bound insoluable form Fe (III) to a soluble form Fe(II), allowing it to be released from iron binding proteins. We have searched the genomes of many bacteria for a similar system and have discovered that many bacteria have MCOs. We wanted to test the idea that the bacteria MCOs we have identified may be involved in iron uptkae. If so, it would represent a huge step forward in understanding this important process and could lead to products for prevention or better treatment of infectious disease. We chose the disease causing bacterium Pseudomonas aeruginosa for our study. We have shown that the MCO has ferroxidase activity (Fe(III)>Fe(II), we have made a mutation in the MCO gene had have shown that the bacterium lacking MCO will not grow under certain conditions. These conditions are consistent with a defect in iron uptake. We have identified but not characterised several other key compnents of this iron uptake system. In the proposed work we wish to investigate all of the components of this iron uptake system in this important pathogen, and to initiate studies in other bacteria pathogens.Read moreRead less
Genetic Dissection Of The Biogenesis And Function Of Type IV Fimbriae Of Pseudomonas Aeruginosa
Funder
National Health and Medical Research Council
Funding Amount
$407,545.00
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. This pathogen, and a number of other important infectious bacteria use surface filaments, called fimbriae, like grappling hooks to attach to the cells of the body and to move across host tissues. These fimbriae are produced in response to environmental conditions, and are assembled by a pro ....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. This pathogen, and a number of other important infectious bacteria use surface filaments, called fimbriae, like grappling hooks to attach to the cells of the body and to move across host tissues. These fimbriae are produced in response to environmental conditions, and are assembled by a process that is also used in the export of toxins and other pathogenic molecules. This project will characterise genes which specify and control this system, as a means to design better treatments against such bacteria, many of which are resistant to antibiotic treatment.Read moreRead less
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.