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A Review on Enterocin DD14, the Leaderless Two-Peptide Bacteriocin with Multiple Biological Functions and Unusual

Rabia Ladjouzi1, Elodie Dussert1, Radja Teiar1

  • 1UMR Transfrontalière BioEcoAgro, INRAe 1158, ICV-Institut Charles Viollette, University Lille, INRAE, University Liège, UPJV, YNCREA, University Artois, University Littoral Côte d'Opale, F-59000 Lille, France.

Antibiotics (Basel, Switzerland)
|July 29, 2023
PubMed

Insights

Enterocin DD14, a bacteriocin from human Enterococcus faecalis, shows broad-spectrum antimicrobial and antiviral activities. It also enhances antibiotic efficacy against MRSA and reduces inflammation, suggesting therapeutic potential.

Area of Science:

  • Microbiology
  • Bacteriocin Research
  • Therapeutic Agent Development

Background:

  • Enterocin DD14 (EntDD14) is a novel two-peptide leaderless bacteriocin (LLB) produced by the human commensal strain *Enterococcus faecalis* 14.
  • Bacteriocins are ribosomally synthesized antimicrobial peptides with potential applications in medicine and biotechnology.

Purpose of the Study:

  • To characterize the antimicrobial, antiviral, and immunomodulatory properties of EntDD14.
  • To investigate the genetic basis and transport mechanism of EntDD14 production.
  • To explore the therapeutic potential of EntDD14, particularly in combination with antibiotics.

Main Methods:

  • Antimicrobial and antiviral activity assays against various Gram-positive pathogens and cell lines.
  • Genome sequencing and annotation of *E. faecalis* 14 using bioinformatics tools like Bagel4.
  • In vitro and in vivo studies using a mouse model to assess EntDD14's potentiation of antibiotic activity against MRSA.
  • Analysis of pro-inflammatory cytokine secretion in human intestinal cells.

Main Results:

  • EntDD14 demonstrated potent activity against *Listeria monocytogenes*, *Clostridium perfringens*, *Enterococcus faecalis*, and *Staphylococcus aureus*.
  • EntDD14 significantly potentiated the efficacy of erythromycin, kanamycin, and methicillin against MRSA in vitro and in vivo.
  • EntDD14 exhibited antiviral properties and reduced the secretion of pro-inflammatory IL-6 and IL-8 in Caco-2 cells.
  • The EntDD14 cluster was identified, and its transport was shown to involve a complex system of PH-domain proteins (DdE/DdF) and an ABC transporter (DdGHIJ).

Conclusions:

  • EntDD14 is a promising multifunctional bacteriocin with significant antimicrobial, antiviral, and immunomodulatory effects.
  • The unique transport mechanism highlights novel strategies for bacteriocin export and self-protection.
  • EntDD14 represents a valuable model for studying two-peptide LLBs and holds potential for therapeutic applications, including combating antibiotic-resistant bacteria.
Keywords:
Enterocin DD14 (EntDD14)antibacterial and antiviral propertiesleaderless bacteriocin (LLB)specific transport

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