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Researchers from Hebrew University publish new studies and findings in the area of drug resistance
2009 AUG 3 - (NewsRx.com) -- According to recent research from Jerusalem, Israel, "Multidrug transporters provide a survival strategy for living organisms. As expected given their central role in survival, these transporters are ubiquitous, and in many genomes, several genes coding for putative transporters have been identified." "However, in an organism such as Escherichia coli mutations in genes coding for transporters other than the major AcrAB-TolC multidrug efflux transporter have only a marginal effect on phenotype. Thus, whether the physiological role of the transporters identified is indeed drug export has been questioned. We show here that the minor effect of single mutations is due to the overlapping functionality of several transporters. This was revealed by generating multiple chromosomal deletion mutations in genes coding for transporters that share the same substrate and testing their effect on the resistance phenotype. In addition, complementation studies imply that AcrAB-TolC confers robust resistance provided that single-component transporters in the plasma membrane are functional. This finding supports the contention that hydrophobic drugs are removed in a 2-stage process: AcrAB-TolC removes substrates from the periplasmic space, while single-component transporters remove them from the cell. The overlapping specificities of the transporters ensure coverage of a wide range of xenobiotics and provide robustness in the response to environmental stress," wrote N. Tal and colleagues, Hebrew University. The researchers concluded: "This strategy also confers evolvability to the organism by reducing constraints on change and allowing the accumulation of nonlethal variation." Tal and colleagues published their study in Proceedings of the National Academy of Sciences of the United States of America (A coordinated network of transporters with overlapping specificities provides a robust survival strategy. Proceedings of the National Academy of Sciences of the United States of America, 2009;106(22):9051-9056). For additional information, contact S. Schuldiner, Hebrew University of Jerusalem, Alexander A Silberman Institute Life Science, Dept. of Biology Chemical, IL-91904 Jerusalem, Israel. Publisher contact information for the journal Proceedings of the National Academy of Sciences of the United States of America is: National Acad Sciences, 2101 Constitution Avenue NW, Washington, DC 20418, USA. Keywords: Israel, Jerusalem, Drug Development, Drug Resistance, Escherichia coli, Physiology, Therapy, Treatment, Hebrew University. This article was prepared by Anti-Infectives Week editors from staff and other reports. Copyright 2009, Anti-Infectives Week via NewsRx.com.
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