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. <i>Acinetobacter baumannii</i> 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 <i>A. baumannii</i>, 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 <i>A. baumannii</i> (MDRAB) isolates. Interestingly, <i>in vitro</i>, this endolysin could not only inhibit <i>A. baumannii</i>, but also that of other strains, such as <i>Escherichia coli</i> and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA). We found that lethal <i>A. baumannii</i> sepsis mice could be effectively rescued <i>in vivo</i> 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 <i>A. baumannii</i>-associated nosocomial infections.