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Intrinsic resistance of Enterococcus faecalis strains to ΦEf11 phage endolysin is associated with the presence of

Hongming Zhang1, Roy H Stevens2

  • 1Laboratory of Oral Infectious Diseases, Kornberg School of Dentistry, Temple University, Philadelphia, PA, 19140, USA.

Archives of Virology
|November 9, 2020
PubMed

Insights

Bacteriophage endolysins show promise against multidrug-resistant pathogens. However, some Enterococcus faecalis strains resist the ΦEf11 ORF28 lysin due to the presence of a ΦEf11 prophage, indicating lysogenic conversion confers resistance.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Bacteriophage-encoded murein hydrolases (endolysins) are explored for combating multidrug-resistant pathogens.
  • The ΦEf11 ORF28 lysin exhibits significant antimicrobial activity against Enterococcus faecalis, including vancomycin-resistant strains (VRE).
  • A subset of E. faecalis strains displays intrinsic resistance to the ORF28 lysin, with the underlying mechanism previously unexplained.

Purpose of the Study:

  • To investigate the cause of disparate ORF28 lysin sensitivity among E. faecalis strains.
  • To determine the role of the ΦEf11 prophage in lysin resistance.
  • To elucidate the mechanism of lysin resistance in E. faecalis.

Main Methods:

  • Comparative analysis of ΦEf11 prophage presence in lysin-sensitive and lysin-resistant E. faecalis strains.
  • Experimental lysogenic conversion: curing lysogenic strains and lysogenizing non-lysogenic strains.
  • Phenotypic assessment of lysin sensitivity before and after prophage manipulation.

Main Results:

  • Intrinsic lysin insensitivity in E. faecalis is strongly associated with the presence of a ΦEf11 prophage.
  • Strains harboring ΦEf11 genes showed significantly higher rates of lysin insensitivity (68%) compared to strains lacking these genes (9%).
  • Experimental manipulation confirmed that lysogenic conversion is responsible for the transition from lysin sensitivity to resistance.

Conclusions:

  • Lysin resistance in E. faecalis is mediated by lysogenic conversion, where the presence of the ΦEf11 prophage confers resistance.
  • Understanding this mechanism is crucial for the effective therapeutic application of endolysins against E. faecalis infections.
  • This study identifies a key factor determining the efficacy of phage lysins as antimicrobial agents.

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