Efflux mediated multidrug resistance in Staphylococcus aureus

Funded Activity 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 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.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $738,056.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Medical Bacteriology

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

antimicrobial resistance | bacterial pathogen | drug efflux pump | drug transport | multidrug resistance | multiply-resistant staphylococci | nosocomial infection | staphylococcus aureus | transmembrane protein

Related Links