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A Novel Enterococcus Phage Endolysin Lys22 with a Wide Host Range Against Mixed Biofilm of Enterococcus faecalis,

Ziqin Yang1, Xue Du2, Nannan Hu1

  • 1Department of Pathogenobiology, College of Basic Medical Science, Jilin University, Changchun 130021, China.

Pathogens (Basel, Switzerland)
|October 29, 2025
PubMed

Insights

Lys22, an endolysin, effectively targets multidrug-resistant bacteria like Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter baumannii. This phage derivative inhibits biofilms and combats mixed infections, offering a novel antimicrobial strategy.

Area of Science:

  • Microbiology and Infectious Diseases
  • Antimicrobial Resistance
  • Bacteriophage Therapy

Background:

  • Multidrug-resistant (MDR) bacterial pathogens, including Enterococcus faecalis, Staphylococcus aureus, and Acinetobacter baumannii, are a growing global health concern, frequently causing hospital-acquired infections.
  • These bacteria form resilient biofilms that contribute to treatment failures by resisting conventional antibiotics and immune responses.
  • Bacteriophages and their derivatives, such as endolysins, are emerging as promising alternatives to combat antibiotic-resistant bacteria.

Purpose of the Study:

  • To evaluate the efficacy of Lys22, an endolysin derived from an enterococcus phage, against key multidrug-resistant bacterial pathogens.
  • To assess Lys22's activity in inhibiting simple and complex bacterial biofilms.
  • To investigate Lys22's potential therapeutic application in treating mixed bacterial infections.

Main Methods:

  • Cloning and characterization of Lys22, an endolysin with a broad host range.
  • In vitro assessment of Lys22's inhibitory effects on biofilms formed by E. faecalis, S. aureus, and A. baumannii.
  • Analysis of virulence gene expression (e.g., agrA, sarA, icaA, asa1, cylA, gelE, OmpA, lpsB) following Lys22 treatment.
  • In vivo efficacy testing of Lys22 in a zebrafish embryo model of dual or triple bacterial infections.

Main Results:

  • Lys22 demonstrated broad-spectrum activity against E. faecalis, S. aureus, and A. baumannii.
  • Lys22 significantly inhibited the formation and structure of both simple and complex biofilms in vitro.
  • Lys22 treatment led to the downregulation of key virulence genes in the tested bacterial species.
  • Lys22 provided significant protection against lethal dual and triple infections in the zebrafish embryo model.

Conclusions:

  • Lys22 is a potent endolysin effective against clinically relevant multidrug-resistant bacteria and their biofilms.
  • Lys22 exhibits a dual mechanism of action by inhibiting biofilm formation and downregulating virulence factors.
  • Lys22 shows promise as a therapeutic agent for treating complex, polymicrobial infections caused by resistant pathogens.
Keywords:
Acinetobacter baumanniiEnterococcus faecalisStaphylococcus aureuscomposite biofilmsendolysinmultidrug resistance

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