Efficacy of Artilysin® Art-175 against resistant and persistent Acinetobacter baumannii

Bacteriophage-encoded endolysins have shown promise as a novel class of antibacterials with a unique mode of action, i.e. peptidoglycan degradation. However, Gram-negative pathogens are generally not susceptible due to their protective outer membrane. The concept of Artilysin®s overcomes this barrier. Artilysin®s are optimized, engineered fusions of selected endolysins with specific outer membrane destabilizing peptides. Artilysin® Art-175 comprises a modified variant of endolysin KZ144 with an N-terminal fusion to SMAP-29. Previously, we have shown the high susceptibility ofP. aeruginosafor Art-175. Here, we report that Art-175 is highly bactericidal against stationary phase cells of multidrug-resistantAcinetobacter baumannii, even resulting in a complete elimination of large inocula (≥ 10(8)CFU/ml). Besides actively-dividing cells, also persisters are killed. Instantaneous killing ofA. baumanniiupon contact with Art-175 could be visualized after immobilization of the bacteria in a microfluidic flow cell. Effective killing of a cell takes place through osmotic lysis after peptidoglycan degradation. The killing rate is enhanced by the addition of 0.5 mM EDTA. No resistance development against Art-175 under selection pressure or no cross-resistance with existing resistance mechanisms could be observed. In conclusion, Art-175 represents a highly active Artilysin® against bothA. baumanniiandP. aeruginosa, two of the most life-threatening pathogens of the order of thePseudomonadales.

Jaar van publicatie:2016

BOF-keylabel:ja

IOF-keylabel:ja

BOF-publication weight:3

CSS-citation score:3

Authors from:Government, Higher Education

Toegankelijkheid:Open