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Bacteriophages that infect Gram-negative bacteria as source of signal-arrest-release motif lysins

Marco Túlio Pardini Gontijo1, Pedro Marcus Pereira Vidigal2, Maryoris Elisa Soto Lopez3

  • 1Departamento de Genética, Evolução, Microbiologia e Imunologia, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Rua Monteiro Lobato 255, Campinas, São Paulo, 13083-862, Brazil.

Research in Microbiology
|December 21, 2020
PubMed

Insights

Bacteriophage lysins show promise for treating multidrug-resistant Gram-negative bacterial infections. This study identifies evolutionary markers for signal peptide-containing lysins, aiding in the development of novel antimicrobial strategies.

Area of Science:

  • Microbiology
  • Genomics
  • Bacteriophage Therapy

Background:

  • Multidrug-resistant (MDR) Gram-negative bacteria pose a significant treatment challenge.
  • Bacteriophage-derived lytic enzymes (lysins) offer a potential therapeutic solution.
  • The impermeable outer membrane of Gram-negative bacteria hinders lysin efficacy, but signal peptides can facilitate outer membrane permeation.

Purpose of the Study:

  • To investigate the evolutionary markers of signal peptide-containing lysins in bacteriophages.
  • To identify potential lysin candidates for combating MDR Gram-negative bacterial infections.

Main Methods:

  • Genomic analysis of 309 bacteriophages infecting clinically relevant Gram-negative pathogens.
  • Identification and characterization of lysins with signal peptides and signal-arrest-release motifs.
  • Phylogenetic analysis of lysin distribution.

Main Results:

  • 265 putative lysins were identified across the analyzed bacteriophage genomes.
  • 17 lysins (6.41%) possessed signal-arrest-release motifs and 41 (15.47%) had cleavable signal peptides.
  • Lysin diversity correlated with bacteriophage pan-genome clustering, suggesting co-evolution.
  • Signal peptide-containing lysins were monophyletically distributed, indicating divergent selection for holin-independent activity.

Conclusions:

  • Evolutionary markers for signal peptide-containing lysins were identified.
  • A subset of identified lysins (58 candidates) are suitable for further in vitro testing against MDR bacteria.
  • Findings support the development of bacteriophage lysins as a novel therapeutic approach against challenging bacterial infections.
Keywords:
Antibiotic substituteBacteriophage-derived lytic enzymeESKAPEEnzybioticNosocomial pathogen

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