The endolysin of the Acinetobacter baumannii phage vB_AbaP_D2 shows broad antibacterial activity

Abstract

Summary The emergence and rapid spread of multidrug‐resistant bacteria has induced intense research for novel therapeutic approaches. In this study, the Acinetobacter baumannii bacteriophage D2 (vB_AbaP_D2) was isolated, characterized and sequenced. The endolysin of bacteriophage D2, namely Abtn‐4, contains an amphipathic helix and was found to have activity against multidrug‐resistant Gram‐negative strains. By more than 3 log units, A. baumannii were killed by Abtn‐4 (5 µM) in 2 h. In absence of outer membrane permeabilizers, Abtn‐4 exhibited broad antimicrobial activity against several Gram‐positive and Gram‐negative bacteria, such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, Enterococcus and Salmonella. Furthermore, Abtn‐4 had the ability to reduce biofilm formation. Interestingly, Abtn‐4 showed antimicrobial activity against phage‐resistant bacterial mutants. Based on these results, endolysin Abtn‐4 may be a promising candidate therapeutic agent for multidrug‐resistant bacterial infections.

A Novel Acinetobacter baumannii Bacteriophage Endolysin LysAB54 With High Antibacterial Activity Against Multiple Gram-Negative Microbes

“…Several natural known endolysins also exhibited antibacterial activity against Gram-negative bacteria in the absence of OMPs, such as OBPgp279 against P. aeruginosa , PlyF307 and LysAB21 against A. baumannii ( Lai et al., 2011 ; Walmagh et al., 2012 ; Lood et al., 2015 ). It is demonstrated with increasing evidence that several endolysins are active against multiple Gram-negative bacteria, and few of them are reported active against Gram-positive pathogens in vitro , such as Abtn-4 ( Yuan et al., 2020 ), LysSAP26 ( Kim et al., 2020a ), and LysSS ( Kim et al., 2020b ). Such lysins with broad host-range are commonly contain a lysozyme or glycoside hydrolase catalytic activity, which cleaves the β-1,4-glycosidic linkage between N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) in peptidoglycans that is generally shared by various bacteria ( Ghose and Euler, 2020 ).…”

“…However, treatment bacteria with outer membrane permeabilizers (OMPs), such as citric acid, trichloroethane (CHCl 3 ), Triton X-100, and EDTA, can improve the antibacterial activity of endolysins and conquer the hindrance presented by the outer membrane of Gram-negative bacteria ( Helander and Mattila-Sandholm, 2000 ; Briers et al., 2007 ; Briers et al., 2011 ; Briers et al., 2014 ; Yang et al., 2015b ; Guo et al., 2017 ). In this context, several endolysins have showed improved or synergistic bactericidal activity against MDR A. baumannii and P. aeruginosa in the presence of OMPs, including LysSS ( Kim et al., 2020b ), Abtn-4 ( Yuan et al., 2020 ), LysPA26 ( Guo et al., 2017 ), PlyA ( Yang et al., 2015b ), ABgp46 ( Oliveira et al., 2016 ), and OBPgp279 ( Walmagh et al., 2012 ). However, lysins with OMP-independent antibacterial activity against Gram-negative microbes still un-adequately addressed since few of them are demonstrated effective in animal infection models.…”

Lysins breaking down the walls of Gram-negative bacteria, no longer a no-go

“…A. baumannii appears as the most sensitive species for currently unknown reasons [7,8]. Some of these lysins have an unusually broad spectrum covering both Gram-negative and Gram-positive strains [9,10]. Based on analyses of truncated lysin variants, there is a growing consensus that the mechanism of action of many of these lysins is based on a self-promoted uptake mechanism induced by a Cterminal amphipathic helix that interacts with the OM, followed by active peptidoglycan degradation by the Nterminal enzymatic domain.…”

Characterization of a Lytic Bacteriophage vB_EfaS_PHB08 Harboring Endolysin Lys08 against Enterococcus faecalis Biofilms

“…Recently, phages and their derivates have been re-considered as effective tools for treating bacterial infections, particularly those caused by multi-drug-resistant pathogens [ 30 , 51 , 52 ]. The emergence of resistance in Enterococci against antibiotics of glycopeptides (vancomycin and teicoplanin) has attracted people’s attention [ 53 , 54 ].…”

“…Phages and their derivatives, such as endolysins, are also effective for reducing and/or eradicating bacterial biofilms [ 26 , 27 , 28 ]. However, few studies have examined the efficacy of phages and/or phage-derivatives in controlling biofilms formed by Gram-positive bacteria, including E. faecalis , in vitro [ 29 , 30 ].…”