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

Abstract

With widespread abuse of antibiotics, bacterial resistance has increasingly become a serious threat. Acinetobacter baumannii has emerged as one of the most important hospital-acquired pathogens worldwide. Bacteriophages (also called “phages”) could be used as a potential alternative therapy to meet the challenges posed by such pathogens. Endolysins from phages have also been attracting increasing interest as potential antimicrobial agents. Here, we isolated 14 phages against A. baumannii, determined the lytic spectrum of each phage, and selected one with a relatively broad host range, named vB_AbaP_PD-6A3 (PD-6A3 for short), for its biological characteristics. We over-expressed and purified the endolysin (Ply6A3) from this phage and tested its biological characteristics. The PD-6A3 is a novel phage, which can kill 32.4% (179/552) of clinical multidrug resistant A. baumannii (MDRAB) isolates. Interestingly, in vitro, this endolysin could not only inhibit A. baumannii, but also that of other strains, such as Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). We found that lethal A. baumannii sepsis mice could be effectively rescued in vivo by phage PD-6A3 and endolysin Ply6A3 intraperitoneal injection. These characteristics reveal the promising potential of phage PD-6A3 and endolysin Ply6A3 as attractive candidates for the control of A. baumannii-associated nosocomial infections.

Modulation of Endolysin LysECD7 Bactericidal Activity by Different Peptide Tag Fusion

“…However, several isolates were resistant to LysECD7-8his in different species (Figure 1). In terms of the number of strains tested, this study of the bactericidal action of endolysin is among the largest studies currently published [24,39]. The reason for the wide mode of action of endolysins remains unknown.…”

Identification and Characterization of New Bacteriophages to Control Multidrug-Resistant Pseudomonas aeruginosa Biofilm on Endotracheal Tubes

“…Genomic bioinformatics analysis allowed identifying the endolysin gene on all bacteriophages. Commonly, this enzyme is responsible for the lytic ability of tailed bacteriophages ( Wu et al, 2019 ). In addition, several open reading frames could only be annotated as coding for hypothetical proteins and thus with an unknown function, something that is common in bacteriophage studies ( Guo et al, 2019 ).…”

Gram-Negative Bacterial Lysins

“…Additional A. baumannii specific lysins have been identified and recombinantly expressed, such as LysABP-01, PlyAB1, ABgp46, and Ply6A3, which may be promising and may potentially be developed for the treatment of MDR infections of A. baumannii (Table 1) [22,47,48,50]. Lysin LysABP-01 isolated from A. baumannii lytic bacteriophage ABP-01 has bactericidal activity against A. baumannii, E. coli and P. aeruginosa [47].…”

“…In the presence of membrane permeabilizing agents such as citric acid and malic acid, ABgp46 was active against additional Gram-negative pathogens such as P. aeruginosa and Salmonella enterica serovar Typhimurium. Lysin Ply6A3 produced by bacteriophage PD-6A3 was shown to kill 70% of MDR A. baumannii strains and protect 70% of mice in a lethal A. baumannii sepsis challenge model [50].…”