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Broad Bactericidal Activity of the Myoviridae Bacteriophage Lysins LysAm24, LysECD7, and LysSi3 against Gram-Negative

Nataliia P Antonova1,2, Daria V Vasina3, Anastasiya M Lendel4

  • 1N.F. Gamaleya Federal Research Centre for Epidemiology and Microbiology, Ministry of Health of the Russian Federation, 123098 Moscow, Russia. northernnatalia@gmail.com.

Viruses
|March 24, 2019
PubMed

Insights

Bacteriophage lysins show potent activity against drug-resistant Gram-negative bacteria. These novel enzymes, LysAm24, LysECD7, and LysSi3, effectively kill ESKAPE pathogens, offering new hope against antibiotic resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • The rise of multidrug-resistant Gram-negative pathogens poses a significant global health threat, potentially leading to a post-antibiotic era.
  • Bacteriophage lysins, enzymes that degrade bacterial cell walls, are explored as potential alternatives to conventional antibiotics.
  • Limited data exists on the efficacy of bacteriophage lysins against a broad spectrum of Gram-negative bacteria.

Purpose of the Study:

  • To evaluate the in vitro bactericidal activity of three newly characterized bacteriophage endolysins (LysAm24, LysECD7, and LysSi3) against Gram-negative clinical isolates.
  • To investigate the potential of these lysins as therapeutic agents in combating antibiotic-resistant infections.

Main Methods:

  • Cloning and purification of three putative Myoviridae bacteriophage endolysins: LysAm24, LysECD7, and LysSi3.
  • Characterization of the purified lysins' enzymatic properties.
  • In vitro activity assays against a panel of Gram-negative clinical isolates, including ESKAPE pathogens (Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, Enterococcus faecium, and Staphylococcus aureus) and Salmonella typhi.

Main Results:

  • All three tested lysins (LysAm24, LysECD7, and LysSi3) demonstrated broad-spectrum lytic activity against Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli, and Salmonella typhi.
  • Effective eradication of bacterial cells was achieved at concentrations below 50 μg/mL, reducing bacterial populations by over five orders of magnitude.
  • Lysins with diverse domain organizations and predicted mechanisms of action exhibited comparable efficacy.

Conclusions:

  • LysAm24, LysECD7, and LysSi3 are effective bactericidal agents against key Gram-negative pathogens.
  • These bacteriophage endolysins represent promising candidates for the development of novel antimicrobial therapies to combat multidrug-resistant infections.
  • Further research into these lysins could lead to new strategies to overcome the challenge of the declining antibiotic arsenal.
Keywords:
ESKAPEMyoviridaebacteriophage-derived lytic enzymebacteriophagesendolysinenzybioticsin vitro activity

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