Polyamine binding to a bacterial efflux pump involved in antimicrobial resistance

What is it about?

The aim of this work was to use highly intense light produced by a synchrotron facility to detect binding of the polyamine compound spermidine to a protein called AceI from the pathogenic bacterium Acinetobacter baumannii, which is a leading cause of hospital-acquired infections. AceI is an efflux pump in the cell membrane of A. baumannii that extrudes the antiseptic compound chlorhexidine from the cell. Efflux pumps are one of the major mechanisms that bacteria use for resistance against antimicrobial agents such as chlorhexidine. Because chlorhexidine is an industrially produced compound, it is not a natural substrate of AceI. This work was the start of our investigation into whether polyamine compounds such as spermidine are naturally occurring substrates of AceI.

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Photo by Myriam Zilles on Unsplash

Photo by Myriam Zilles on Unsplash

Why is it important?

This work reports the first experimental evidence that was obtained to demonstrate that polyamines are naturally occurring substrates of the PACE (proteobacterial antimicrobial compound efflux) family of bacterial multidrug efflux proteins. It is important to understand the structure, function, ligand interaction and molecular mechanism of bacterial efflux proteins in order to design strategies to combat antimicrobial resistance of pathogenic bacteria.