Real-Time Molecular Typing Systems In Infection Control: Design And Effectiveness
Funder
National Health and Medical Research Council
Funding Amount
$82,554.00
Summary
MRSA is a major cause of hospital-acquired infection. Molecular typing identifies how a patient managed to contract MRSA in the hospital, and if the strain they have is particularly dangerous. This study will develop a rapid typing protocol then implement it routinely, to determine whether providing this information to infection control staff in a more timely fashion will lead to reduced MRSA infections in hospitals.
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
Identification And Analysis Of Novel Replication Initiation Factors In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$311,789.00
Summary
Multi-drug resistant Golden staph is a serious medical problem around the world because strains are often resistant to commonly used treatments; new drugs are therefore urgently required. DNA replication is a fundamental process that is essential for the survival of all cellular organisms. This project aims to identify and characterise novel factors involved in DNA replication in Golden staph, which represent potential drug targets.
Novel Compounds For Use As Inhibitors Of Virulence Of Human Pathogens
Funder
National Health and Medical Research Council
Funding Amount
$220,500.00
Summary
There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interferin ....There is growing concern over the emergence of multi-drug resistant strains of bacteria which are no longer treatable with the current generation of antibiotics. This highlights the urgent need for development of the next generation of therapeutic agents to supplement or replace the current antibiotics. Our research team has identified a class of compounds which are naturally produced by a marine alga that may be effective in the control of bacterial pathogens. These compounds work by interfering with the way many pathogens regulate the production of virulence traits. Some bacteria are able to signal members of their population by the specific uptake and recognition, through a receptor protein, of chemical cues they secrete into the environment. Accumulation of these cues or signals triggers expression of the genes that code for the virulence traits. Moreover, one particular class of these signal response proteins has been identified in many pathogens and has been shown to regulate protease production and production of a protective extracellular slime layer called a capsule. If one or more of these traits can be blocked, then the virulence of the bacterium can be reduced. We have preliminary data which demonstrates that the algal compounds do in fact prevent the expression of virulence traits and thus should be useful as new agents for the treatment of disease. The causative agents of cholera and severe gatroenteritis, Vibrio cholerae and V. parahaemolyticus respectively, have one or the other of these virulence traits, but the pathogen Vibrio vulnificus has all three and therefore is an excellent model pathogen. We propose to explore the ability of the algal compounds to specifically shut down expression of virulence factors with a long term aim for the development of these compounds as novel antimicrobial therapies for the post-antibiotic era.Read moreRead less