Mutagenesis of a bacteriophage lytic enzyme PlyGBS significantly increases its antibacterial activity against group B

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Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi
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Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi

Published on: September 28, 2022

Qi Cheng1, Vincent A Fischetti

  • 1The Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

Applied Microbiology and Biotechnology
|December 23, 2006
PubMed

Insights

Researchers engineered a bacteriophage enzyme, PlyGBS, to combat Group B streptococci (GBS) infections. Hyperactive mutants showed significantly increased lytic activity, offering a potential alternative to intrapartum antibiotic prophylaxis for preventing neonatal GBS disease.

Area of Science:

  • Microbiology
  • Biotechnology
  • Molecular Biology

Background:

  • Group B streptococci (GBS) are a primary cause of neonatal meningitis and sepsis globally.
  • Intrapartum antibiotic prophylaxis (IAP) is the standard preventative measure for GBS colonization during pregnancy.
  • Concerns regarding antibiotic resistance in GBS necessitate alternative prevention strategies.

Purpose of the Study:

  • To develop enhanced bacteriophage lytic enzymes for reducing vaginal GBS colonization.
  • To identify and characterize hyperactive mutants of the PlyGBS enzyme with improved lytic activity.

Main Methods:

  • Employing various DNA mutagenesis techniques to generate PlyGBS mutants.
  • Assessing the lytic activity and spectrum of engineered mutants against GBS.
  • Evaluating the efficacy of a hyperactive mutant (PlyGBS90-1) in a mouse vaginal colonization model.

Main Results:

  • Several hyperactive PlyGBS mutants were identified, containing only the N-terminal endopeptidase domain.
  • These mutants exhibited 18-28 fold increases in specific lytic activity compared to wild-type PlyGBS.
  • A single dose of PlyGBS90-1 reduced GBS colonization in mice by approximately 4 logs.

Conclusions:

  • Engineered PlyGBS mutants demonstrate significantly enhanced lytic activity against GBS.
  • These hyperactive mutants show potential as a safe and effective alternative to IAP for preventing neonatal GBS infections.

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