The respiratory pathogen P. aeruginosa, one of the most common causes of hospital-acquired pneumonia, adds three small molecules to an ordinary lung protein, turning it into a gateway for access to human cells, according to researchers from the Emory University School of Medicine, the University of Virginia, and Universidad de las Islas Baleares in Mallorca, Spain.
The scientists discovered that P. aeruginosa leverages a lung protein called elongation factor-Tu (EF-Tu) in order to infect its host.
“EF-Tu is presumed to be an essential protein, and it’s performing these moonlighting functions as well,” said co-author Joanna Goldberg of Emory University.
Using a host of techniques, including mass spectrometry, site-directed mutagenesis of key residues in the protein, and genetic loss of function/gain of function studies, investigators found that P. aeruginosa only makes small changes to EF-Tu to get it to mimic this powerful ligand. P. aeruginosa transfers three methyl groups to a lysine on EF-Tu, giving it a structure similar to common bacterial epitope phosphorylcholine (ChoP) and allowing it to fit in the PAFR receptor in the way ChoP does.
The modification of EF-Tu enables the bacterium to adhere to human cells and invade, said researchers, who also believe it seems to be involved in virulence in mouse models.
