Trapping and killing superbugs with novel peptide nanonets

National University of Singapore (NUS) pharmaceutical scientists have developed synthetic peptide nanonets for treating infections by bacteria strains resistant to last-resort antibiotics.

In nature, trap-and-kill is a common immune defense mechanism employed by various species, including humans. In response to the presence of pathogens, peptides are released from host cells and they promptly self-assemble in solution to form cross-linked nanonets, which then entrap the bacteria and render them more vulnerable to antimicrobial components.

Several research groups have explored synthetic biomimetics of nanonets as an avenue for addressing the global healthcare challenge of widespread antibiotic resistance. However, most prominent studies in the field only yielded disjointed short nanofibrils restricted to the bacterial surfaces and are incapable of physically immobilizing the bacteria. Additionally, these designs were lacking in control over the initiation of the self-assembly process.

A research team led by Associate Professor Rachel EE from the Department of Pharmacy, NUS has designed short ?-hairpin peptides of 15 to 16 residues that are capable of self-assembling into nanonets selectively in response to lipopolysaccharide or lipoteichoic acid, which are integral membrane components unique to bacteria.

This specificity towards bacteria is an appealing attribute not yet achieved in the field. The peptide nanonets displayed both trapping and antimicrobial killing functionalities, thus offering a direct upgrade from the trap-only nanonets in nature as well as synthetic designs reported in the field. This opens up opportunities for modulating the activity spectrum of the material.

Image source: National University of Singapore.