| 研究実績の概要 |
Multidrug resistance (MDR) is a growing problem in the treatment of bacterial infections, where bacterial cells develop resistance to multiple antibiotics. One of the major mechanisms responsible for MDR is the efflux of antibiotics by RND-type multidrug efflux pumps. These pumps are capable of recognizing and extruding a wide range of structurally diverse antibiotics. Understanding the structure and function of RND-type efflux pumps is crucial for developing strategies to combat MDR, including the design of new antibiotics that can evade efflux pumps or the development of efflux pump inhibitors that can restore the efficacy of existing antibiotics. In this research, we focussed on these RND-type efflux pumps. We have successfully cloned RND-type efflux pumps from several pathogenic organisms. We have also investigated the roles of outer membrane proteins and the PAP/RND interactions. We have also investigated specific mutations in RND-type efflux pumps from hospital isolates. The results have shown that amino acid substitutions play an important role in acquired and increased resistance against specific antibiotics. We have also obtained interesting information regarding the trimeric dynamics of certain efflux pumps and the tripartite formation of multiple unstudied pumps from different microorganisms, which we are currently investigating further for publication.
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