A Novel Phage PD-6A3, and Its Endolysin Ply6A3, With Extended Lytic Activity Against Acinetobacter baumannii

Area of Science:

• Microbiology
• Infectious Diseases
• Biotechnology

Background:

• Antibiotic resistance is a growing global health threat, particularly from hospital-acquired pathogens like Acinetobacter baumannii.
• Bacteriophages (phages) and their derived endolysins are emerging as potential alternatives to antibiotics for combating resistant bacteria.

Purpose of the Study:

• To isolate and characterize novel phages and their endolysins effective against multidrug-resistant Acinetobacter baumannii (MDRAB).
• To evaluate the therapeutic potential of a selected phage (PD-6A3) and its endolysin (Ply6A3) against MDRAB infections both in vitro and in vivo.

Main Methods:

• Isolation and characterization of 14 phages targeting Acinetobacter baumannii.
• Determination of phage lytic spectrum and selection of phage vB_AbaP_PD-6A3 (PD-6A3) for further study.
• Over-expression and purification of endolysin Ply6A3 from phage PD-6A3.
• In vitro testing of PD-6A3 and Ply6A3 against various bacterial strains, including MDRAB, Escherichia coli, and methicillin-resistant Staphylococcus aureus (MRSA).
• In vivo efficacy study using a mouse model of Acinetobacter baumannii sepsis.

Main Results:

• Phage PD-6A3 demonstrated activity against 32.4% of clinical MDRAB isolates.
• Endolysin Ply6A3 exhibited inhibitory activity against Acinetobacter baumannii, Escherichia coli, and MRSA in vitro.
• Both phage PD-6A3 and endolysin Ply6A3 were effective in rescuing mice from lethal Acinetobacter baumannii sepsis when administered intraperitoneally.

Conclusions:

• Phage PD-6A3 is a novel agent with a broad lytic spectrum against MDRAB.
• Endolysin Ply6A3 shows potential as a broad-spectrum antimicrobial agent.
• Phage PD-6A3 and endolysin Ply6A3 represent promising candidates for controlling Acinetobacter baumannii-associated nosocomial infections.