|Project Theme||Structural biology on efflux transport machineries to understand multi-drug resistance|
|Project Theme (short)||Efflux transport machineries|
|Principal Investigator||Satoshi Murakami|
|Affiliation||Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology|
|Backgrounds||- Drug resistance, the reduction in effectiveness of a drug such as an antimicrobial or an anti-cancer drug, is the main cause of hospital-acquired infection
- Drug resistance is also an emerging threat in fish breeding and stockbreeding industries
- One important mechanism of drug resistance is reduced drug accumulation by pumping out the drugs across the multidrug efflux transporters
|Highlights||- The structure of multidrug efflux transporter MexB in Pseudomonas aeruginosa has been determined
- Comparative analyses of Escherichia coli transporters AcrB and AcrD have revealed differences in selectivity of charged drugs
|Outline|| Drug resistance, the reduction in effectiveness of a drug such as an antimicrobial or an anti-cancer drug, is an emerging threat worldwide. One of the mechanisms by which microorganisms or tumor cells exhibit resistance is reduced drug accumulation by increasing active efflux (pumping out) of the drugs across the multidrug efflux transporters on the cell surface. Since gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa possess an outer membrane outside the cytoplasmic membrane, their drug efflux is carried out by the transport machinery composed of a multidrug efflux transporter on the cytoplasmic membrane, an outer-membrane channel and a membrane-fusion protein. We already reported crystal structures of AcrB, a principal multidrug efflux transporter in E. coli with and without substrates.
In this project, we will elucidate the entire structure of the transport machinery in action to understand its functions in detail.