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.
Microparticles And Selective Trait Dominance In Multidrug Resistant Cancers
Funder
National Health and Medical Research Council
Funding Amount
$478,115.00
Summary
Multidrug resistance (MDR) is the cause of treatment failure in 90% of patients with metastatic cancer. We recently discovered a novel resistance mechanism in which microparticles provide a vehicle for intercellular transfer of MDR. We now report that MP play an even more significant role in conferring MDR, by the ñre-templatingî of cancer cell traits. This has considerable potential for translation into clinical outcomes with the identification of alternative drug targets and therapeutics for t ....Multidrug resistance (MDR) is the cause of treatment failure in 90% of patients with metastatic cancer. We recently discovered a novel resistance mechanism in which microparticles provide a vehicle for intercellular transfer of MDR. We now report that MP play an even more significant role in conferring MDR, by the ñre-templatingî of cancer cell traits. This has considerable potential for translation into clinical outcomes with the identification of alternative drug targets and therapeutics for the circumvention of MDR clinically.Read moreRead less
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.
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.
Understanding Multidrug Resistance In Cancer: Identification Of The Substrate And Inhibitor Binding Sites In P-glycoprotein
Funder
National Health and Medical Research Council
Funding Amount
$284,343.00
Summary
Cancers expressing the multidrug transporter P-glycoprotein (P-gp) are resistant to chemotherapy. The clinical impact of P-gp is so large that the National Cancer Institute (USA) “profiles” all anticancer drugs for transport by P-gp, primarily because the mechanism of drug binding and transport by P-gp is unknown. The aim of this proposal is to understand the molecular details of how drugs bind to and interact with P-gp, a major step in our understanding of P-gp mediated chemotherapy resistance.
Understanding And Targeting Acquired Chemoresistance In High-grade Serous Ovarian Cancer
Funder
National Health and Medical Research Council
Funding Amount
$527,824.00
Summary
We recently discovered a mutation in recurrent high-grade serous ovarian cancer that causes profound overexpression of the multidrug resistance pump, MDR1 (Patch et al Nature 2015). In this study I will explore approaches to reverse drug resistance caused by this mutation in recurrent ovarian cancer with a view to utilising alternative treatments to improve patient outcomes.
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.
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.