Shared Molecular Mechanisms but Diverging Roles in Physiology and Medicine

Multi-drug efflux systems are ubiquitous in all domains of life. They are requisite in normal physiology in man, altering the pharmacology of medicines, and providing protection to the brain and other sites from toxic xenobiotics. Linked to human health, with the increasing prevalence of drug resistance in disease-causing pathogens, where efflux systems are important mediators of resistance. Multi-drug resistance in bacteria, yeast and the malarial parasite is of particular concern. Its occurrence has steadily risen in the past decades to become one of the major health concerns of our modern society. Multi-drug efflux systems present a frequently used and flexible means for eukaryotic and prokaryotic cells alike to resist our arsenal of once potent agents, gaining time to gather other mechanisms of resistance. On the other hand, the role of drug efflux and membrane transporters in human disease is also increasingly understood. Efflux transporters have been found in central roles in human disease - from drug toxicity due to interpatient variation in pharmacology-related pumps, to disease due to lack of efflux of endogenous substrates, to a potential role in cancer treatment failure or in cancer biology.

It is from the research of the many active participants of the highly appreciated and fruitful past GRCs that our knowledge on the molecular mechanisms of transport and multi-drug recognition, genetic regulation, and pharmacological modulation has gained considerable momentum. Increasingly, we understand that complex mechanisms regulate accumulation and extrusion of xenobiotics as well as therapeutic agents in eukaryotic and prokaryotic cells.

The 5th meeting on Multi-Drug Efflux Systems, will focus on the role of efflux systems in health and disease. The keynote lectures will be held by recognized leaders in the field. Sessions will be organized such that each session will be introduced by an expert scientist giving a brief overview of current knowledge relating in vitro and clinical data to particular efflux systems. We will address questions on the significance of efflux on the multidrug resistance phenotype in context of the role of uptake mechanisms, the role of efflux in eukaryotic systems, control of gene expression, and regulation on the protein level including post-translational modification. Aspects on structure and mechanism of multi-drug resistance pumps and a dedicated session on methods how to study drug transporters including imaging techniques. Concurrently, this conference will also address the multi-drug uptake systems that coexist with efflux systems in determining substrate accumulation. Sessions on the role of drug transporters in pharmacology and pharmacogenomics and on approaches to control multi-drug resistance in man and bacteria will complete the conference.

An old Japanese saying, "On Ko Chi Shin", means that we must understand the old in order to understand the new. Already the ancient organisms were equipped with multi-drug efflux systems– yet now we need to understand their structure, function, and role in the modern age. Ample time will be given for exchange of knowledge during discussions as well as opportunities for junior scientist to present their latest data. The broad yet focused range of topics will give many of us the opportunity to lay foundation for future work by including learning from the past in the ongoing quest to tackle the problem of multidrug resistance in bacterial infections and cancer.