Phage Endolysin LysP108 Showed Promising Antibacterial Potential Against Methicillin-resistant Staphylococcus aureus

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.

Polyphosphate Kinase Is Required for the Processes of Virulence and Persistence in Acinetobacter baumannii

“…A BacLight Live/Dead staining assay was performed to further evaluate the bacterial retention states after treatment with 40× MIC (640 μg/mL) of Amp for 8 h ( 37 ). The bacteria were collected at 12,000 rpm at 4°C for 5 min and washed twice with PBS.…”

The Holin-Endolysin Lysis System of the OP2-Like Phage X2 Infecting Xanthomonas oryzae pv. oryzae

“…Previous reports have shown that endolysin added from the outside results in cell death, which may be due to two reasons. One is that endolysin can directly attack the molecular structure of Gram-positive bacteria, which have no outer membrane [56,57]. The other is that endolysins with antibacterial effects in vitro are generally applied to bacteria together with outer membrane permeabilizers [58][59][60], as Gram-negative bacteria have an outer membrane, preventing antibacterial effects [54].…”

Characterization of Klebsiella pneumoniae bacteriophages, KP1 and KP12, with deep learning-based structure prediction

“…Phage-encoded endolysin has been a promising antibacterial agent because of its advantages compared to phage itself such as non-proliferation, rapid bacterial cell lysis, low bacterial resistance, clear mode of action, easy-to-engineer, anti-biofilm property, and synergistic activity with different antibacterial agents ( Schmelcher et al, 2012 ; Abdelrahman et al, 2021 ; Lu et al, 2021 ). To date, several endolysin-based therapies are in clinical trials to demonstrate its safety and efficacy ( Kim et al, 2018 ; Wang et al, 2021 ), indicating its prevalence as a major antibiotics alternative to treat multidrug-resistant bacteria.…”