30 Mar 2018 Abracts

Combating Multi-drug Resistant Gram-Negative Pathogens: Artilysins

Allison Eastham '18

Briers et al. addressed the public health threat caused by multidrug-resistant bacteria, and attempted to develop a novel approach to combat bacterial infections. Endolysins represent a potential avenue of investigation. These enzyme-based antibacterials kill Gram-positive bacteria via specific cell wall hydrolysis. Briers et al., however noted the issue of Gram-negative pathogens when considering endolysins as an avenue for treatment, due to the impermeable lipopolysaccharide layer surrounding their cell wall. As such, they developed an approach to engineer endolysins as outer membrane-permeating endolysins (Artilysins), which rendered them highly bactericidal against Gram-negative pathogens. When they combined a polycationic nonapeptide and a modular endolysin, they found they were able to kill these strains in vitro with a 4 to 5 log reduction within 30 minutes. They showed that the activity of Artilysins can be further enhanced by the presence of a linker of increasing length between the peptide and endolysin, or by a combination of both polycationic and hydrophobic/amphipathic peptides. Briers et al. discovered the Artilysin’s mode of action using time-lapse microscopy, which showed that they pass through the outer membrane to degrade the peptidoglycan with subsequent cell lysis. They also found that Artilysins were effective in vitro and in vivo.

Exercise Science Presentation

Charlie Shervheim '18 and Nick Powell '18