A research group led by Associate Professor Seiji Yamazaki at SANKEN, Osaka University and Professor Kunihiko Nishino at SANKEN, Osaka University has clarified the spatial characteristics of inhibitor binding sites in the bacterial drug efflux pump. The research group’s findings provide a clear pathway for the development of new drugs to avert a large-scale drug-resistant bacterial pandemic.
Although our research group has previously elucidated that drug efflux pumps in bacteria contribute significantly to the development of bacterial drug resistance (Nature 480:565-9, 2011, Nature 500:102-6, 2013, etc.), drug efflux pump inhibitors have not yet been commercialized, and the characteristics of the inhibitor binding site However, drug efflux pump inhibitors have not yet been commercialized, and the characteristics of the inhibitor binding sites have not been elucidated.
In this study, the research group clarified that the spatial space above, in the middle, and below the inhibitor binding site is important for inhibitor binding by analyzing a large number of mutant pumps with artificially mutated amino acid residues. In fact, the research group is now developing new inhibitors based on the results of this study, which is expected to be put into practical use as soon as possible.

For more information (https://www.sanken.osaka-u.ac.jp/hot_topics/topics_20221028/ )

The results of this research were published on Thursday, October 27, 2022 in the American scientific journal Antimicrobial Agents and Chemotherapy” (online) on Thursday, October 27, 2022.
Title: “Spatial Characteristics of the Efflux Pump MexB Determine Inhibitor Binding”
Author(s): Seiji Yamasaki, Naoki Koga, Martijn Zwama, Keisuke Sakurai, Ryosuke Nakashima, Akihito Yamaguchi, Kunihiko Nishino
DOI: https://doi.org/10.1128/aac.00672-22

This research is supported by the Ministry of Education, Culture, Sports, Science and Technology, “Network Joint Research Center for Materials and Devices (CORE-Lab) Program”, “CORE²-A Laboratory of the Crossover Alliance for Human This research was supported by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) “CORE Lab”, “Crossover Alliance for Creating the Future with People, Knowledge and Materials: CORE²-A Lab”, JST “Center of Innovation (COI)”, “CREST”, JSPS “Grant-in-Aid for Scientific Research (B), Challenging (Budding Researchers), Young Scientists”, Nippon Foundation and Osaka University “Countermeasures against Infectious Diseases Project”, and AMED “Project to Promote the Development of Innovative Drugs for Emerging and Re-emerging Infections”. The project was supported by the Nippon Foundation and Osaka University’s “Countermeasures to Combat Infectious Diseases Project” and the AMED’s “Research Program for the Development of Innovative Drugs for Emerging and Re-emerging Infectious Diseases”.