New lab research pinpoints drug resistance details
plays a critical role in drug resistance, which may open up new
avenues for laboratory research that may result in the enhancement
of existing therapies for Cancer and infectious diseases.
In describing the X-ray crystalline structure of the Escherichia coli multidrug resistance protein E (EmrE), a multidrug transporter that actively expels a wide variety of drugs from the cell, scientists have at last can see, on a cellular level how the mechanism of drug resistance works.
EmrE is a prototype of a Small Multidrug Resistance (SMR) family, the smallest transporters in nature.
Scientists from The Scripps Research Institute used X-ray crystallography, to detail the structure of EmrE. The research revealed that a transporter composed of two chemically identical polypeptides assembled to form a dimer.
In addition, scientists noticed that when formed, the two asymmetrical, subunits of the transporter created a single direction pathway removing drug molecules from the cell, a recurring theme in other structural studies of different transporter families.
Lead researcher Geoffrey Chang, an associate professor in the Scripps Research Department of Molecular Biology and a member of the Skaggs Institute for Chemical Biology suggested that EmrE could form even more complex structures to bind with drugs.
Although it remains to be confirmed, these complex structures could increase the efficiency of drug recognition and efflux.
"Determining the structure of integral membrane proteins is an exciting frontier in molecular structural biology," Chang said in the study.
"By describing the crystalline structure of EmrE, we are coming closer to understanding the molecular structural basis of multidrug resistance, which has become a serious challenge in the development of effective therapeutic agents to treat a number of infectious diseases," he said.
Treating these emerging types of bacteria can be far more expensive than treating normal infections, and the World Health Organisation estimates the total cost of treating all hospital-borne antibiotic resistant bacterial infections at $10 billion (€8 4 billion) a year.
With modern transportation and open borders, these types of bacteria are spread far more easily than in the past and now have the potential of moving from hospital wards into global populations in a matter of weeks.
This new study, published in the journal Science is a promising avenue for particularly addressing the problem of multidrug-resistant strains that cause common diseases such as tuberculosis, gonorrhoea, and hospital-acquired staphylococcal infections.
EmrE is responsible for the bacteria's ability to resist a variety of commonly prescribed antibiotic treatments, including tetracycline and erythromycin.
Bacteria have evolved many different transporters to remove foreign compounds from the cell, and it has become well accepted in science that multidrug resistance systems are present in all cells.
EmrE recognises and transports compounds with few common structural features and different electric charges, extruding various drugs across the bacteria's cell membrane by exchanging several protons for each drug molecule through a specific pathway.
