Investigations into the killing activity of an antimicrobial peptide active against extensively antibiotic-resistant K. pneumoniae and P. aeruginosa

July 28, 2017

Title

Investigations into the killing activity of an antimicrobial peptide active against extensively antibiotic-resistant K. pneumoniae and P. aeruginosa

Author

Hessel van der Weidea, 1, Jlenia Brunettib, 1, Alessandro Pinib, Luisa Braccib, Chiara Ambrosinib, Pietro Lupettic, Eugenio Paccagninic, Mariangela Gentilec, Andrea Berninid, Neri Niccolai, Denise Vermeulen-de Jongh, Irma A.J.M. Bakker-Woudenberg, Wil H.F. Goessens, John P. Hays, Chiara Falciani

Year

2017

Journal

Biochimica et Biophysica Acta (BBA) - Biomembranes

Abstract

SET-M33 is a multimeric antimicrobial peptide active against Gram-negative bacteria in vitro and in vivo. Insights into its killing mechanism could elucidate correlations with selectivity. SET-M33 showed concentration-dependent bactericidal activity against colistin-susceptible and resistant isolates of P. aeruginosa and K. pneumoniae. Scanning and transmission microscopy studies showed that SET-M33 generated cell blisters, blebs, membrane stacks and deep craters in K. pneumoniae and P. aeruginosa cells. NMR analysis and CD spectra in the presence of sodium dodecyl sulfate micelles showed a transition from an unstructured state to a stable α-helix, driving the peptide to arrange itself on the surface of micelles. SET-M33 kills Gram-negative bacteria after an initial interaction with bacterial LPS. The molecule becomes then embedded in the outer membrane surface, thereby impairing cell function. This activity of SET-M33, in contrast to other similar antimicrobial peptides such as colistin, does not generate resistant mutants after 24 h of exposure, non-specific interactions or toxicity against eukaryotic cell membranes, suggesting that SET-M33 is a promising new option for the treatment of Gram-negative antibiotic-resistant infections.

Instrument

J-815

Keywords

Circular dichroism, Secondary structure, Vesicle interactions, Biochemistry