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

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Abstract

The use of bacteriophage-encoded murein hydrolases (endolysins) is being actively explored as a means of controlling multidrug-resistant pathogens. Previously, we isolated and characterized one such enzyme, the phage ΦEf11 ORF28 lysin, which demonstrated profound antimicrobial activity against many strains of Enterococcus faecalis. Although the lysin is eminently active against many vancomycin-resistant enterococal (VRE) strains, and displays lower minimum inhibitory concentrations than vancomycin against vancomycin-sensitive strains, there is a subset of E. faecalis strains that is not affected by the lysin. Currently, there is no explanation for the disparate sensitivity to ORF28 lysin among E. faecalis strains. In the present investigation, we show that the intrinsic insensitivity of the insusceptible strains to the lysin is associated with the presence of a ΦEf11 prophage. Of the strains harboring phage ΦEf11 genes (N = 28), 68% were insensitive to the lysin, whereas 91% of the strains (N = 75) lacking detectable ΦEf11 genes demonstrated lysin sensitivity. Furthermore, curing a lysin-resistant, lysogenic E. faecalis strain resulted in a lysin-sensitive derivative, whereas lysogenizing a wild-type non-lysogenic strain converted it from lysin sensitivity to lysin resistance. Our results suggest that lysin resistance comes about through lysogenic conversion of non-lysogenic, lysin-sensitive strains.

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Acknowledgements

This work utilized NIAID’s suite of preclinical services for in vitro assessment (contract no. 75N93019D00011/75N93019F00 131). The authors are indebted to Dr. Lynn Hancock for his critical reading of our manuscript.

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Supported by internal funding from Temple University Kornberg School of Dentistry.

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

    Hongming Zhang & Roy H. Stevens

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Both authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by both authors. Manuscript was drafted by RHS Both authors read and approved the final manuscript.

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Zhang, H., Stevens, R.H. Intrinsic resistance of Enterococcus faecalis strains to ΦEf11 phage endolysin is associated with the presence of ΦEf11 prophage. Arch Virol 166, 249–258 (2021). https://doi.org/10.1007/s00705-020-04861-7

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