Structural mechanisms of Acinetobacter baumannii multidrug efflux pumps
EMSL Project ID
50691
Abstract
Acinetobacter baumannii has emerged as one of the most problematic and highly antibiotic-resistant pathogens. A. baumannii infections in military personnel injured in Iraq and Afghanistan were so common that this bacterium was termed "Iraqibacter". This bacterium displays high level resistance to a broad range of antimicrobial agents. The majority of A. baumannii strains are carbapenem resistant and resistance to the last resort antibiotics, colistin and tigecycline is increasing. Recently, the WHO has listed carbapenem-resistant A. baumannii as the first-priority pathogen for R&D of new antibiotics. Bacterial multidrug efflux pumps are widely distributed in many pathogens and confer resistance to structurally diverse antimicrobials. Among various types of efflux transporters, members of the resistance-nodulation-cell division (RND) superfamily are the most important in mediating antibiotic resistance in Gram-negative bacteria. Our long-term goal is to control the emergence and spread of antibiotic-resistant Acinetobacter. The specific targets are these A. baumannii RND-type multidrug efflux pumps, which plays a key role in antibiotic resistance and biofilm formation. We have expressed and purified these efflux pumps. We have also embedded these apo efflux pumps in nanodiscs for structural studies using cryo-EM single particle imaging (see Fig. 1). The main goal of this proposal is to elucidate the structures and fundamental mechanisms that govern multiple antibiotic recognition and extrusion. We will resolve the atomic resolution structures of the apo and drug-bound structures of these Acinetobacter multidrug efflux pumps.
Project Details
Start Date
2019-04-22
End Date
2020-02-12
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members