Bactericidal Effect of a Novel Phage Endolysin Targeting Multi-Drug-Resistant Acinetobacter baumannii

Background/Objectives: Infections with antibiotic-resistant Gram-negative pathogens represent a major global threat to public health. Acinetobacter baumannii is a highly important nosocomial pathogen causing severe and life-threatening infections, like pneumonia, wound infections, or sepsis. It is often resistant even against last-resort antibiotics, such as carbapenems, and can persist in healthcare settings. Artilysin ® s are a novel class of endolysins targeted against multidrug-resistant bacteria. Methods: Antibacterial activity of Art-Top3 was determined by broth microdilution, in vitro assays and in the Galleria mellonella infection model. The toxicity of Art-Top3 on red blood cells, endothelial and epithelial cells was analyzed using the MTT assay. Results: Here, we report on a new Artilysin ® Art-Top3 that is active against A. baumannii and led to a 10 5 -fold reduction in viable A. baumannii after five minutes of exposure. Art-Top3 showed activity against A. baumannii biofilms in static and dynamic experimental infection models. Furthermore, upon infection with carbapenem-resistant A. baumannii patient isolates, Art-Top3 was able to rescue human primary cells in vitro and larvae of Galleria mellonella in an in vivo infection model. Art-Top3 did not lyse human red blood cells and showed activity in human serum, indicating a low toxicity and high stability of Art-Top3 in vitro. Conclusion: Our findings collectively establish that Art-Top3 might be a candidate for novel therapeutic strategies of infections caused by multidrug-resistant A. baumannii pathogens.