Novel bacteriophage lysin with broad lytic activity protects against mixed infection by Streptococcus pyogenes and

Daniel B Gilmer1, Jonathan E Schmitz, Chad W Euler

  • 1Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York, USA.

Insights

A novel bacteriophage lysin, PlySs2, demonstrates broad-spectrum activity against dangerous Gram-positive pathogens like MRSA and Streptococcus pyogenes. This stable and effective therapeutic shows promise in combating antibiotic resistance.

Area of Science:

  • Microbiology
  • Biochemistry
  • Therapeutics

Background:

  • Antibiotic resistance in Gram-positive pathogens like Methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pyogenes (group A Streptococcus [GrAS]) necessitates novel therapeutic strategies.
  • The emergence of resistance to existing antibiotics poses a significant threat to public health, driving the search for alternative treatments.

Purpose of the Study:

  • To identify and characterize a novel bacteriophage lysin with broad lytic activity against clinically significant Gram-positive bacteria.
  • To evaluate the stability, efficacy, and resistance potential of the identified lysin, PlySs2, as a potential therapeutic agent.

Main Methods:

  • Identification and purification of the bacteriophage lysin PlySs2 from Streptococcus suis.
  • Assessment of PlySs2's lytic activity spectrum against various Gram-positive pathogens, including MRSA and S. pyogenes.
  • Evaluation of PlySs2's stability under different temperature and storage conditions.
  • In vitro and in vivo efficacy studies using bacteremia models and MIC determination.
  • Analysis of resistance development to PlySs2 compared to mupirocin.

Main Results:

  • PlySs2 exhibited broad lytic activity against a wide range of Gram-positive bacteria, including MRSA, vancomycin-intermediate S. aureus (VISA), S. pyogenes, and Listeria species.
  • The lysin demonstrated remarkable stability at various temperatures and after multiple freeze-thaw cycles.
  • In vitro, PlySs2 significantly reduced MRSA and S. pyogenes growth and showed a low minimum inhibitory concentration (MIC) for MRSA.
  • A single dose of PlySs2 provided significant protection in a murine bacteremia model.
  • No resistance developed to PlySs2 upon serial exposure, unlike mupirocin.

Conclusions:

  • PlySs2 is a potent, stable, and broad-spectrum bacteriophage lysin with significant therapeutic potential against critical Gram-positive pathogens.
  • Its ability to overcome existing resistance mechanisms and lack of induced resistance make PlySs2 a promising candidate for novel antibiotic therapies.

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