2023 Multi-Drug Efflux Systems: Targeting the Mechanisms and Regulation of Multi-Drug Transporters for Advancing Health during a Pandemic GRC/GRS

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Project Summary Multidrug resistance caused by active drug efflux from cells is one of the major clinical impediments in anti- cancer chemotherapy and treatment of infectious diseases. New surveillance data by the World Health Organization reveals widespread antibiotic resistance in some of the world's most common, and potentially most dangerous, pathogens including those causing diarrheal and respiratory diseases, malaria and tuberculosis. The growing threat of drug-resistant pathogens raises the prospect of a world without effective antimicrobials, where patients are left vulnerable to previously treatable infectious diseases. Multidrug efflux systems have evolved to protect microorganisms and humans from harmful xenobiotics and toxic metabolites. They regulate absorption, distribution, and excretion of xenobiotics, and in humans, protect sanctuary tissues by regulating the drug permeability of the blood-brain, blood-placenta and blood–testis barriers. In addition, transporters are also major players in dictating responses to drugs, from pharmacological efficacy to toxicity, and are involved in host-pathogen interactions. Thus, a more complete understanding of multidrug efflux systems is of paramount important for the design of more effective treatments with improved patient outcomes. This proposal requests partial support for the Gordon Research Conference (GRC) and Gordon Research Seminar (GRS) on Multi-Drug Efflux Systems to be held in Galveston, Texas, March 25 – March 31, 2023. The primary goal of this conferences is to bring together researchers from two traditionally isolated fields, the prokaryotic and eukaryotic transporter fields, working across a variety of disciplines (microbiology, chemistry, pharmacology, medicine, and clinical research), to learn from each other. Nine sessions of oral presentations, and four poster sessions will foster scientific interactions between new investigators, leaders in the field, and colleagues working in academia, the pharmaceutical and biotechnology industries. The second goal is to disseminate technological advances and transformative approaches. Sessions will highlight recent innovations in the understanding of structure-function relations, the identification of the drug binding sites, and drug-efflux mechanics, and the pharmacological targeting of transporters including novel drug delivery strategies. The long-term goal is to develop more specific and more potent drugs that inhibit, modulate or evade the multifaceted efflux systems. Further emphasis will be on the regulation of efflux systems mediated by local and global regulators and the multilayered control of gene expression in response to specific environmental cues. The third goal is to mentor early career scientists, integrate women and scientists from minority backgrounds, and provide a learning environment and support system critical for development of future leaders of the field. Overall, this conference will foster discussions at the frontiers of science in multidrug efflux systems for reversing multidrug resistance and advancing global health.