A bacteriophage endolysin that eliminates intracellular streptococci
- University of Maryland, College Park, United States
- Carnegie Mellon University, United States
- The Rockefeller University, United States
- United States Department of Agriculture, United States
Abstract
PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial cell membranes and clears intracellular Spy in a dose-dependent manner. Quantitative studies using model membranes establish that PlyCB interacts strongly with phosphatidylserine (PS) whereas its interaction with other lipids is weak, suggesting specificity for PS as its cellular receptor. Neutron reflection further substantiates that PlyC penetrates bilayers above a PS threshold concentration. Crystallography and docking studies identify key residues that mediate PlyCB-PS interactions, which are validated by site-directed mutagenesis. This is the first report that a native endolysin can translocate epithelial membranes, thus substantiating the potential of PlyC as an antimicrobial for Spy in the extra- and intracellular milieu and as a scaffold for engineering other functionalities.
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Human subjects: For primary epithelial cell cultures, the experimental protocol received Institutional Review Board approvals from both the Rockefeller University (VAF-0621-1207) and the Weill Cornell Medical College (nos. 0803009695 and 0806009857). Individual patient consent for the use of tissue in research applications was obtained prior to the surgical procedure.
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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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A bacteriophage endolysin that eliminates intracellular streptococci
eLife 5:e13152.
https://doi.org/10.7554/eLife.13152
