Molecular basis for recognition of the Group A Carbohydrate backbone by the PlyC streptococcal bacteriophage endolysin

Harley King, Sowmya Ajay Castro, Amol Arunrao Pohane, Cynthia M. Scholte, Vincent A. Fischetti, Natalia Korotkova, Daniel C. Nelson, Helge C. Dorfmueller

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Endolysins are peptidoglycan (PG) hydrolases that function as part of the bacteriophage (phage) lytic system to release progeny phage at the end of a replication cycle. Notably, endolysins alone can produce lysis without phage infection, which offers an attractive alternative to traditional antibiotics. Endolysins from phage that infect Gram-positive bacterial hosts contain at least one enzymatically active domain (EAD) responsible for hydrolysis of PG bonds and a cell wall binding domain (CBD) that binds a cell wall epitope, such as a surface carbohydrate, providing some degree of specificity for the endolysin. Whilst the EADs typically cluster into conserved mechanistic classes with welldefined active sites, relatively little is known about the nature of the CBDs and only a few binding epitopes for CBDs have been elucidated. The major cell wall components of many streptococci are the polysaccharides that contain the polyrhamnose (pRha) backbone modified with species-specific and serotype-specific glycosyl side chains. In this report, using molecular genetics, microscopy, flow cytometry and lytic activity assays, we demonstrate the interaction of PlyCB, the CBD subunit of the streptococcal PlyC endolysin, with the pRha backbone of the cell wall polysaccharides, Group A Carbohydrate (GAC) and serotype c-specific carbohydrate (SCC) expressed by the Group A Streptococcus and Streptococcus mutans, respectively.

Original languageEnglish
Pages (from-to)2385-2397
Number of pages13
JournalBiochemical Journal
Issue number12
StatePublished - Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 The Author(s).

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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