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Antimicrobial Activity of Plectasin NZ2114 in Combination with Cell Wall Targeting Antibiotics Against VanA-Type

Elena B M Breidenstein1, Patrice Courvalin1, Djalal Meziane-Cherif1

  • 1Department of Microbiology, Unité des Agents Antibactériens, Institut Pasteur , Paris, France .

Microbial Drug Resistance (Larchmont, N.Y.)
|March 19, 2015
PubMed

Insights

Antimicrobial peptide plectasin NZ2114 shows synergy with teicoplanin, moenomycin, and dalbavancin against vancomycin-resistant Enterococcus faecalis. These combinations may target different stages of bacterial cell wall synthesis, offering new therapeutic strategies.

Area of Science:

  • Microbiology
  • Pharmacology
  • Biochemistry

Background:

  • Antimicrobial peptide plectasin exhibits activity against resistant bacteria.
  • Vancomycin-resistant Enterococcus faecalis (VRE) poses a significant clinical challenge.
  • Plectasin's efficacy against VRE is less understood compared to other resistant strains.

Purpose of the Study:

  • To evaluate the synergistic activity of plectasin NZ2114 in combination with cell wall-targeting antibiotics against vancomycin-resistant Enterococcus faecalis (VRE).
  • To investigate the mechanisms underlying observed synergistic interactions.
  • To explore potential novel therapeutic strategies for VRE infections.

Main Methods:

  • Disk agar-induction, double-disk assay, fractional inhibitory concentration (FIC) index determination, and time-kill curve analyses were employed.
  • Combinations of plectasin NZ2114 with various cell wall synthesis inhibitors were tested against VanA-type VRE.
  • Further synergistic interactions between other cell wall antibiotics were assessed.

Main Results:

  • Plectasin NZ2114 demonstrated synergistic effects when combined with teicoplanin, moenomycin, and dalbavancin against VRE.
  • Synergy was not observed with vancomycin, telavancin, penicillin G, bacitracin, ramoplanin, daptomycin, or fosfomycin.
  • Teicoplanin and moenomycin showed broad synergy with other antibiotics, suggesting involvement in peptidoglycan transglycosylation inhibition.

Conclusions:

  • Plectasin NZ2114 can potentiate the activity of specific cell wall-targeting antibiotics against VRE.
  • The observed synergies, particularly with teicoplanin and moenomycin, likely involve the inhibition of peptidoglycan transglycosylation.
  • These findings suggest that combinations targeting different stages of cell wall synthesis may offer effective therapeutic options against VRE.

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