Pseudomonas aeruginosa is one tough nut to crack, but a new paper coming out in mBio sheds some light on how that cracking might be done, and adds to our knowledge of an opportunistic pathogen that strikes in homes and hospital wards every day.
Unfortunately for patients, P. aeruginosa is able to resist many types of antibiotics and sometimes develops pan-resistance, which enables it to overcome all available therapies. Its secret is in its porin proteins: the cell takes nascent porin proteins and folds the majority of them into practically impermeable two-domain porins. Only a small minority of nascent proteins are folded into the one-domain, permeable type of porin. Before folding, the nascent porins are identical.
By tinkering with the amino acid sequence of these porins, Sugawara et al. have managed to demonstrate the exact points in the porin that determine its permeability.
“These porins look like a set of pencils, standing on end in a circle, but tilted,” says Howard Shuman, Professor of Microbiology at the University of Chicago and a member of mBio’s board of editors. “By changing something about the angle of the pencils with respect to one another, you can change the pore opening,” says Shuman. Sugawara et al. used site-directed mutagenesis to change certain amino acids in the protein and tested the resulting porin for permeability.
“They obtained a significant mechanistic understanding of how to convert one form of porin to the other to increase outer membrane permeability to antibiotics,” says Shuman. Down the line, he says, this new information about porin structure and amino acid sequence can point the way toward better treatments for P. aeruginosa infections, possibly by changing the conformation of porin proteins to allow previously excluded drugs to pass through the cell membrane.