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

Area of Science:

• Microbiology
• Infectious Diseases
• Drug Discovery

Background:

• Antibiotic-resistant Gram-negative pathogens, particularly Acinetobacter baumannii, pose a significant global health threat.
• Acinetobacter baumannii is a common cause of severe nosocomial infections and often exhibits resistance to last-resort antibiotics like carbapenems.
• Artilysins are a new class of endolysins designed to target multidrug-resistant bacteria.

Purpose of the Study:

• To evaluate the antibacterial activity and safety of a novel Artilysin, designated Art-Top3, against Acinetobacter baumannii.
• To assess the efficacy of Art-Top3 in preclinical models of Acinetobacter baumannii infection.

Main Methods:

• Antibacterial activity was determined using broth microdilution and in vitro assays.
• Efficacy was tested in a Galleria mellonella infection model.
• Toxicity was assessed on human red blood cells and various human cell lines using the MTT assay.

Main Results:

• Art-Top3 demonstrated potent activity, reducing viable Acinetobacter baumannii by 10^5-fold within five minutes.
• The compound effectively targeted Acinetobacter baumannii biofilms in static and dynamic models.
• Art-Top3 rescued human primary cells and Galleria mellonella larvae in infection models, showing no lysis of human red blood cells and stability in human serum.

Conclusions:

• Art-Top3 exhibits significant antibacterial activity against multidrug-resistant Acinetobacter baumannii.
• The low observed toxicity and high stability in vitro suggest Art-Top3 is a promising candidate for therapeutic development.
• These findings support Art-Top3 as a potential novel therapeutic strategy for infections caused by multidrug-resistant Acinetobacter baumannii.