Pathways To Extensive And Pan Antibiotic Resistance In The Globally Disseminated Acinetobacter Baumannii GC2 Clone
Funder
National Health and Medical Research Council
Funding Amount
$865,004.00
Summary
The project will study the evolution of a Acinetobacter baumannii clone that is found all around the world, and has become resistant to most or all of the currently available antibiotics. Resistance has been acquired in a series of steps, and the resistance genes present and the events involved will be used to understand the globalization process. The increased understanding of resistance development should assist in controlling untreatable infections and in preserving antibiotics.
An Ace Up Their Sleeve: Characterisation Of A Novel Family Of Drug Efflux Systems Represented By The Acinetobacter AceI Exporter
Funder
National Health and Medical Research Council
Funding Amount
$400,286.00
Summary
Chlorhexidine is widely used as an antiseptic in products such as skin washes, soaps, mouthwashes, disinfectants and preservatives. We have recently discovered a novel bacterial protein which pumps chlorhexidine out of bacterial cells to make them resistant to this antiseptic agent. This proposal aims to understand this resistance mechanism and to find inhibitors which could be applied in clinical settings to augment the activity of chlorhexidine.
Circuit Breaker: Investigating The Regulatory Circuits Controlling Expression Of Drug Efflux Pumps In The Nosocomial Pathogen Acinetobacter Baumannii
Funder
National Health and Medical Research Council
Funding Amount
$515,244.00
Summary
Hospital-acquired infections caused by drug resistant pathogenic bacteria cost billions of dollars and increase patient pain and morbidity. This research will study the genes controlling multidrug efflux pumps in a major hospital-acquired bacterial pathogen, Acinetobacter baumannii. These efflux pumps make the bacteria resistant to antimicrobials by pumping them out of the cell. The results will allow us to better track drug resistant strains and will inform treatment options.
Multidrug Recognition And Resistance In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$598,978.00
Summary
Strains of Staphylococcus aureus (Golden Staph), resistant to almost all available anti-staphylococcal agents, are responsible for serious infections among patients; in some hospitals such outbreaks reach epidemic proportions. Resistance has emerged to all classes of antimicrobial agents. We will increase our understanding of proteins that confer resistance by pumping multiple antimicrobials out of the cell to ultimately design more effective antibacterials able to bypass such drug pumps.
Molecular Epidemiology Of Antibiotic Resistant Salmonella Enterica Strains Causing Human Disease
Funder
National Health and Medical Research Council
Funding Amount
$493,767.00
Summary
Salmonella infections are responsible for a substantial proportion of reported food poisoning cases caused by bacteria and many of these infections are due to antibiotic resistant strains. Infections caused by antibiotic resistant organisms are hard to treat and generally more severe, of longer duration, and result in longer hospital stays. These strains are mostly acquired from foods, e.g. meats, dairy products, poultry, eggs, and other contaminated food products but can also be derived from ot ....Salmonella infections are responsible for a substantial proportion of reported food poisoning cases caused by bacteria and many of these infections are due to antibiotic resistant strains. Infections caused by antibiotic resistant organisms are hard to treat and generally more severe, of longer duration, and result in longer hospital stays. These strains are mostly acquired from foods, e.g. meats, dairy products, poultry, eggs, and other contaminated food products but can also be derived from other sources. Salmonella strains harboured by food-producing animals are the source of most of the food contamination.Tracing the source of individual resistant strains is essential for eradication and as there are many Salmonella types, some of which are found associated only with specific animals or birds, accurate identification is needed. The proposed work will make this process more accurate by using molecular techniques to unequivocally establish suspected connections and reveal further ones that are difficult to discern using current data and methods. This should decrease the number of infections due to resistant strains.Read moreRead less
Pacing Across The Membrane: Characterising The PACE Family Of Multidrug Efflux Systems
Funder
National Health and Medical Research Council
Funding Amount
$640,815.00
Summary
The World Health Organisation recognises bacterial antimicrobial resistance as one of the major threats to human health worldwide. Multidrug efflux pumps are an important class of resistance proteins that sit in the bacterial cell membrane and move antimicrobials out of the cell. We recently discovered the first new family of multidrug efflux pumps to be described in 15 years. Our project will define the precise resistance functions of this family and identify ways to block their function.
The Current Multidrug Resistant Escherichia Coli Pandemic: Exploring Novel Therapies Against The Predominant Culprit E. Coli ST131.
Funder
National Health and Medical Research Council
Funding Amount
$512,223.00
Summary
Escherichia coli ST131 is a pandemic superbug. Like MRSA, E. coli ST131 infections are resistant to multiple antibiotics and can become life threatening. This study will show how adhesion can be the 'Achilles' heel' of this global pathogen and how blocking E. coli ST131 adhesion offers an alternative therapy for multidrug resistant human infections. As we are left with no effective antimicrobials to treat E. coli ST131 infections, this work will provide novel outcomes that are sorely needed.
Efflux Mediated Multidrug Resistance In Staphylococcus Aureus
Funder
National Health and Medical Research Council
Funding Amount
$738,056.00
Summary
Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph), resistant to almost all available anti-staphylococcal agents, are responsible for serious infections among patients; in some hospitals such outbreaks reach epidemic proportions. In these bacteria, resistance has emerged to all classes of antimicrobial agents, including antibiotics and antiseptics-disinfectants commonly used in the hospital environment, largely due to the acquisition of resistance determinants. These determ ....Strains of the pathogenic bacterium Staphylococcus aureus (Golden Staph), resistant to almost all available anti-staphylococcal agents, are responsible for serious infections among patients; in some hospitals such outbreaks reach epidemic proportions. In these bacteria, resistance has emerged to all classes of antimicrobial agents, including antibiotics and antiseptics-disinfectants commonly used in the hospital environment, largely due to the acquisition of resistance determinants. These determinants encode proteins that provide the bacterial cell with a range of different biochemical mechanisms to evade antibiotic chemotherapy. Specifically, this project seeks to increase our understanding of proteins that confer resistance by pumping structurally-dissimilar antimicrobials out of the cell. The importance of these proteins in the biology of organisms is implied by the fact that an overwhelming majority of the drug targets are membrane proteins. Proteins which recognise such a broad spectrum of compounds are called multidrug resistance (MDR) proteins and present a disturbing clinical threat since the acquisition of one such system by a cell may simultaneously decrease its susceptibility to a number of antimicrobials. Similar MDR pumps are widespread in nature and are credited for resistance to antibiotics and other chemotherapeutic drugs in many pathogenic organisms and in human cancer cells. In this project, we aim to characterise the QacA MDR protein which is involved in pumping many different antimicrobial compounds from staphylococcal cells. We will identify the regions of the QacA MDR protein which bind the compounds and examine how the protein expels them to give resistance. These studies are a prerequisite for the design of more effective antibacterial compounds able to bypass these drug resistance pumps and will also provide fundamental knowledge applicable to the problem of MDR in other infectious diseases and cancer.Read moreRead less
A New Mechanism For Transposition Of Antibiotic Resistance Genes
Funder
National Health and Medical Research Council
Funding Amount
$501,839.00
Summary
Understanding how antibiotic resistance genes are acquired by bacteria is important if we are to understand how bacteria become resistant in so many antibiotics, limiting treatment options. This project will investigate the way a family of insertion sequences captures and then moves resistance genes. This mechanism contributes to resistance in many bacterial pathogens including ones that are resistant to many different antibiotics.
Role Of IS26 In Antibiotic Resistance Gene Recruitment, Dissemination And Expression
Funder
National Health and Medical Research Council
Funding Amount
$457,879.00
Summary
Antibiotic resistance is increasing, compromising the efficacy of front-line antibiotics. Untreatable infections due to bacteria that are resistant to all available antibiotics are being seen more often. To control the spread of resistance, an understanding of how resistance arises and is spread among bacteria is needed. This requires information about how the genetic elements that mobilize them work. This project will study one of the most important of these elements.