AUTHOR=Wang Jing , Liang Siyu , Lu Xiaofeng , Xu Qiu , Zhu Yao , Yu Shenye , Zhang Wanjiang , Liu Siguo , Xie Fang 

TITLE=Bacteriophage endolysin Ply113 as a potent antibacterial agent against polymicrobial biofilms formed by enterococci and Staphylococcus aureus

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1304932

DOI=10.3389/fmicb.2023.1304932

ISSN=1664-302X

ABSTRACT=<p>Antibiotic resistance in <italic>Enterococcus faecium</italic>, <italic>Enterococcus faecalis</italic>, and <italic>Staphylococcus aureus</italic> remains a major public health concern worldwide. Furthermore, these microbes frequently co-exist in biofilm-associated infections, largely nullifying antibiotic-based therapy. Therefore, it is imperative to develop an efficient therapeutic strategy for combating infections caused by polymicrobial biofilms. In this study, we investigated the antibacterial and antibiofilm activity of the bacteriophage endolysin Ply113 <italic>in vitro</italic>. Ply113 exhibited high and rapid lytic activity against <italic>E. faecium</italic>, <italic>E. faecalis</italic>, and <italic>S. aureus</italic>, including vancomycin-resistant <italic>Enterococcus</italic> and methicillin-resistant <italic>S. aureus</italic> isolates. Transmission electron microscopy revealed that Ply113 treatment led to the detachment of bacterial cell walls and considerable cell lysis. Ply113 maintained stable lytic activity over a temperature range of 4–45°C, over a pH range of 5.0–8.0, and in the presence of 0–400 mM NaCl. Ply113 treatment effectively eliminated the mono-species biofilms formed by <italic>E. faecium</italic>, <italic>E. faecalis</italic>, and <italic>S. aureus</italic> in a dose-dependent manner. Ply113 was also able to eliminate the dual-species biofilms of <italic>E. faecium</italic>–<italic>S. aureus</italic> and <italic>E. faecalis</italic>–<italic>S. aureus</italic>. Additionally, Ply113 exerted potent antibacterial efficacy <italic>in vivo</italic>, distinctly decreasing the bacterial loads in a murine peritoneal septicemia model. Our findings suggest that the bacteriophage endolysin Ply113 is a promising antimicrobial agent for the treatment of polymicrobial infections.</p>