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    Bactericidal synergism between phage Endolysin Ply2660 and Cathelicidin LL-37 against Vancomycin-resistant Enterococcus faecalis biofilms (2023)

    Art
    Zeitschriftenartikel / wissenschaftlicher Beitrag
    Autoren
    Zhang, Huihui
    Zhang, Xinyuan
    Liang, Siyu
    Wang, Jing
    Zhu, Yao
    Zhang, Wanjiang
    Liu, Siguo
    Schwarz, Stefan (WE 7)
    Xie, Fang
    Quelle
    NPJ biofilms and microbiomes
    Bandzählung: 9
    Heftzählung: 1
    Seiten: Artikel 16
    ISSN: 2055-5008
    Sprache
    Englisch
    Verweise
    URL (Volltext): https://pubmed.ncbi.nlm.nih.gov/37024490/
    DOI: 10.1038/s41522-023-00385-5
    Pubmed: 37024490
    Kontakt
    Institut für Mikrobiologie und Tierseuchen

    Robert-von-Ostertag-Str. 7-13
    14163 Berlin
    +49 30 838 51843 / 66949
    mikrobiologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Antibiotic resistance and the ability to form biofilms of Enterococcus faecalis have compromised the choice of therapeutic options, which triggered the search for new therapeutic strategies, such as the use of phage endolysins and antimicrobial peptides. However, few studies have addressed the synergistic relationship between these two promising options. Here, we investigated the combination of the phage endolysin Ply2660 and the antimicrobial peptide LL-37 to target drug-resistant biofilm-producing E. faecalis. In vitro bactericidal assays were used to demonstrate the efficacy of the Ply2660-LL-37 combination against E. faecalis. Larger reductions in viable cell counts were observed when Ply2660 and LL-37 were applied together than after individual treatment with either substance. Transmission electron microscopy revealed that the Ply2660-LL-37 combination could lead to severe cell lysis of E. faecalis. The mode of action of the Ply2660-LL-37 combination against E. faecalis was that Ply2660 degrades cell wall peptidoglycan, and subsequently, LL-37 destroys the cytoplasmic membrane. Furthermore, Ply2660 and LL-37 act synergistically to inhibit the biofilm formation of E. faecalis. The Ply2660-LL-37 combination also showed a synergistic effect for the treatment of established biofilm, as biofilm killing with this combination was superior to each substance alone. In a murine peritoneal septicemia model, the Ply2660-LL-37 combination distinctly suppressed the dissemination of E. faecalis isolates and attenuated organ injury, being more effective than each treatment alone. Altogether, our findings indicate that the combination of a phage endolysin and an antimicrobial peptide may be a potential antimicrobial strategy for combating E. faecalis.