AUTHOR=Oliveira Hugo , Vilas Boas Diana , Mesnage Stéphane , Kluskens Leon D. , Lavigne Rob , Sillankorva Sanna , Secundo Francesco , Azeredo Joana 

TITLE=Structural and Enzymatic Characterization of ABgp46, a Novel Phage Endolysin with Broad Anti-Gram-Negative Bacterial Activity

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00208

DOI=10.3389/fmicb.2016.00208

ISSN=1664-302X

ABSTRACT=<p>The present study demonstrates the antibacterial potential of a phage endolysin against Gram-negative pathogens, particularly against multidrug resistant strains of <italic>Acinetobacter baumannii</italic>. We have cloned, heterologously expressed and characterized a novel endolysin (ABgp46) from <italic>Acinetobacter</italic> phage vb_AbaP_CEB1 and tested its antibacterial activity against several multidrug-resistant <italic>A. baumannii</italic> strains. LC-MS revealed that ABgp46 is an <italic>N</italic>-acetylmuramidase, that is also active over a broad pH range (4.0–10.0) and temperatures up to 50°C. Interestingly, ABgp46 has intrinsic and specific anti-<italic>A. baumannii</italic> activity, reducing multidrug resistant strains by up to 2 logs within 2 h. By combining ABgp46 with several organic acids that act as outer membrane permeabilizing agents, it is possible to increase and broaden antibacterial activity to include other Gram-negative bacterial pathogens. In the presence of citric and malic acid, ABgp46 reduces <italic>A. baumannii</italic> below the detection limit (&gt;5 log) and more than 4 logs <italic>Pseudomonas aeruginosa</italic> and <italic>Salmonella typhimurium</italic> strains. Overall, this globular endolysin exhibits a broad and high activity against Gram-negative pathogens, that can be enhanced in presence of citric and malic acid, and be used in human and veterinary medicine.</p>