High avidity drives the interaction between the streptococcal C1 phage endolysin, PlyC, with the cell surface carbohydrates of Group A Streptococcus

Molecular Microbiology, vol. 116, pp. 397–415

Abstract

Endolysin enzymes from bacteriophage cause bacterial lysis by degrading the peptidoglycan cell wall. The streptococcal C1 phage endolysin PlyC, is the most potent endolysin described to date and can rapidly lyse group A, C, and E streptococci. PlyC is known to bind the Group A streptococcal cell wall, but the specific molecular target or the binding site within PlyC remain uncharacterized. Here we report for the first time, that the polyrhamnose backbone of the Group A streptococcal cell wall is the binding target of PlyC. We have also characterized the putative rhamnose binding groove of PlyC and found four key residues that were critical to either the folding or the cell wall binding action of PlyC. Based on our results, we suggest that the interaction between PlyC and the cell wall may not be a high-affinity interaction as previously proposed, but rather a high avidity one, allowing for PlyC's remarkable lytic activity. Resistance to our current antibiotics is reaching crisis levels and there is an urgent need to develop the antibacterial agents with new modes of action. A detailed understanding of this potent endolysin may facilitate future developments of PlyC as a tool against the rise of antibiotic resistance.

Authors 15

1. Sebastian S. Broendum

   Monash University

   Affiliation as printed

   Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology Monash University Melbourne VIC Australia

   Biomedicine Discovery Institute, Department of Microbiology Monash University Melbourne VIC Australia

   Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia

   Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, Australia

2. Brooke K. Hayes

   Monash University

   Affiliation as printed

   Biomedicine Discovery Institute, Department of Microbiology Monash University Melbourne VIC Australia

   Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, Australia

3. Felix Kraus

   Monash University

   Affiliation as printed

   Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology Monash University Melbourne VIC Australia

   Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia

4. James Fodor

   Australian National University · Monash University

   Affiliation as printed

   Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology Monash University Melbourne VIC Australia

   Eccles Institute of Neuroscience, John Curtin School of Medical Research The Australian National University Canberra ACT Australia

   Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia

   Eccles Institute of Neuroscience, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia

5. Ben E. Clifton

   Australian National University

   Affiliation as printed

   Research School of Chemistry Australian National University Acton ACT Australia

   Research School of Chemistry, Australian National University, Acton, ACT, Australia

6. Jeroen D. C. Codée Aachen Department of Bio-organic Synthesis

   Leiden University

   Affiliation as printed

   Department of Bio‐organic Synthesis, Leiden Institute of Chemistry Leiden University Leiden The Netherlands

   Department of Bio-organic Synthesis, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands

7. Blake T. Riley

   CUNY Advanced Science Research Center · Monash University

   Affiliation as printed

   Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology Monash University Melbourne VIC Australia

   Structural Biology Initiative CUNY Advanced Science Research Center New York NY USA

   Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia

   Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY, USA

8. Nyssa Drinkwater

   Monash University

   Affiliation as printed

   Biomedicine Discovery Institute, Department of Microbiology Monash University Melbourne VIC Australia

   Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, Australia

9. Kylie A. Farrow

   Monash University

   Affiliation as printed

   Biomedicine Discovery Institute, Department of Microbiology Monash University Melbourne VIC Australia

   Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, Australia

10. Kirill Tsyganov

    Monash University

    Affiliation as printed

    Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology Monash University Melbourne VIC Australia

    Monash Bioinformatics Platform Monash University Melbourne VIC Australia

    Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia

    Monash Bioinformatics Platform, Monash University, Melbourne, VIC, Australia

11. Ryan D. Heselpoth

    Institute for Bioscience and Biotechnology Research · University of Maryland, College Park

    Affiliation as printed

    Institute for Bioscience and Biotechnology Research University of Maryland, College Park Rockville MD USA

    Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, Rockville, MD, USA

12. Daniel C Nelson

    Institute for Bioscience and Biotechnology Research · University of Maryland, College Park

    Affiliation as printed

    Institute for Bioscience and Biotechnology Research University of Maryland, College Park Rockville MD USA

    Institute for Bioscience and Biotechnology Research, University of Maryland, College Park, Rockville, MD, USA

13. Colin J. Jackson

    Australian National University

    Affiliation as printed

    Research School of Chemistry Australian National University Acton ACT Australia

    Research School of Chemistry, Australian National University, Acton, ACT, Australia

14. Ashley M. Buckle

    Monash University

    Affiliation as printed

    Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology Monash University Melbourne VIC Australia

    Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, Australia

15. Sheena McGowan corresponding

    Monash University

    Affiliation as printed

    Biomedicine Discovery Institute, Department of Microbiology Monash University Melbourne VIC Australia

    Biomedicine Discovery Institute, Department of Microbiology, Monash University, Melbourne, VIC, Australia