Abstract
As a potential antibacterial agent, endolysin can directly lyse Gram-positive bacteria from the outside and does not lead to drug resistance. Considering that XN108 is the first reported methicillin-resistant Staphylococcus aureus (MRSA) strain in mainland China with a vancomycin MIC that exceeds 8 µg mL-1, we conducted a systematic study on its phage-encoded endolysin LysP108. Standard plate counting method revealed that LysP108 could lyse S. aureus and Pseudomonas aeruginosa with damaged outer membrane, resulting in a significant reduction in the number of live bacteria. Scanning electron microscopy results showed that S. aureus cells could be lysed directly from the outside by LysP108. Live/dead bacteria staining results indicated that LysP108 possessed strong bactericidal ability, with an anti-bacterial rate of approximately 90%. Crystal violet staining results implied that LysP108 could also inhibit and destroy bacterial biofilms. In vivo animal experiments suggested that the area of subcutaneous abscess of mice infected with MRSA was significantly reduced after the combined injection of LysP108 and vancomycin in comparison with monotherapy. The synergistic antibacterial effects of LysP108 and vancomycin were confirmed. Therefore, the present data strongly support the idea that endolysin LysP108 exhibits promising antibacterial potential to be used as a candidate for the treatment of infections caused by MRSA.
Highlights
The abuse of antibiotics has led to the frequent emergence of multidrug-resistant superbugs, which make the clinical treatment of infectious diseases difficult (Nathan and Cars, 2014; Blair et al, 2015)
Genomic annotation revealed that the phage P108 encode a putative endolysin, which was named LysP108 (GenBank protein ID: YP_009099525.1)
peptidoglycan cleavage domain (PCD) is responsible for cleaving specific peptidoglycan covalent bond structures, whereas CBD is responsible for adhering to the bacterial cell wall
Summary
The abuse of antibiotics has led to the frequent emergence of multidrug-resistant superbugs, which make the clinical treatment of infectious diseases difficult (Nathan and Cars, 2014; Blair et al, 2015). As natural predators of bacteria, bacteriophages (phages) are used in the treatment of drug-resistant bacterial infections (Kutateladze and Adamia, 2010; Dıé z-Martıń ez et al, 2015). Endolysin is a cell wall hydrolase that plays an important role in the later stage of phage infection (Gerstmans et al, 2018). It can lyse the cell wall from inside the bacteria and help release progeny phages outside the cell (Rodrıǵ uez-Rubio et al, 2013). We have validated the antibacterial effect of LysP108 in vitro and in vivo and explored its potential in combination with antibiotics, thereby providing a new way for solving the increasingly serious problem of bacterial drug resistance
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