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LysJEP8: A promising novel endolysin for combating multidrug-resistant Gram-negative bacteria

Jose Vicente Carratalá1,2,3,4, Neus Ferrer-Miralles1,2,4, Elena Garcia-Fruitós3

  • 1Institute of Biotechnology and Biomedicine, Autonomous University of Barcelona, Barcelona, Spain.

Microbial Biotechnology
|June 12, 2024
PubMed

Insights

A new endolysin, LysJEP8, shows strong potential against multidrug-resistant Gram-negative bacteria like Pseudomonas aeruginosa. This bacteriophage-derived protein effectively reduces bacterial survival and disrupts biofilms, offering a promising alternative to combat antimicrobial resistance.

Area of Science:

  • Microbiology
  • Biotechnology
  • Infectious Diseases

Background:

  • Antimicrobial resistance (AMR) is a critical global health threat, exacerbated by antibiotic overuse.
  • Multidrug-resistant Gram-negative bacteria, including ESKAPE pathogens, pose significant challenges due to high mortality rates.
  • Bacteriophage-derived endolysins represent a novel therapeutic avenue against resistant bacteria.

Purpose of the Study:

  • To introduce and characterize LysJEP8, a novel endolysin from Escherichia phage JEP8.
  • To evaluate LysJEP8's antimicrobial activity against key Gram-negative pathogens.
  • To assess LysJEP8's efficacy in combating bacterial biofilms.

Main Methods:

  • In silico analysis to predict optimal activity conditions.
  • Comparative assessment of LysJEP8's efficacy against ESKAPE pathogens.
  • Evaluation of LysJEP8's performance at varying pH and salt concentrations.
  • Assessment of LysJEP8's biofilm disruption capabilities.

Main Results:

  • LysJEP8 demonstrated significant antimicrobial activity against Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae.
  • The endolysin showed superior bacterial reduction compared to other known endolysins, particularly against P. aeruginosa.
  • Optimal activity was observed at lower pH, with reduced efficacy at physiological salt concentrations.
  • LysJEP8 effectively disrupted P. aeruginosa biofilms.

Conclusions:

  • LysJEP8 is a potent candidate for developing new antibacterial agents against Gram-negative pathogens.
  • Further engineering of LysJEP8 could enhance its therapeutic potential in combating AMR.
  • This endolysin offers a promising alternative to conventional antibiotics for treating resistant infections.

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