PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides

Jeffrey S. Rush, Prakash Parajuli, Alessandro Ruda, Jian Li, Amol Arunrao Pohane, Svetlana Zamakhaeva, Mohammad M. Rahman, Jennifer C. Chang, Artemis Gogos, Cameron W. Kenner, Gérard Lambeau, Michael J. Federle, Konstantin V. Korotkov, Göran Widmalm, Natalia Korotkova

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


The cell wall of the human bacterial pathogen Group A Streptococcus (GAS) consists of peptidoglycan decorated with the Lancefield group A carbohydrate (GAC). GAC is a promising target for the development of GAS vaccines. In this study, employing chemical, compositional, and NMR methods, we show that GAC is attached to peptidoglycan via glucosamine 1-phosphate. This structural feature makes the GAC-peptidoglycan linkage highly sensitive to cleavage by nitrous acid and resistant to mild acid conditions. Using this characteristic of the GAS cell wall, we identify PplD as a protein required for deacetylation of linkage N-acetylglucosamine (GlcNAc). X-ray structural analysis indicates that PplD performs catalysis via a modified acid/base mechanism. Genetic surveys in silico together with functional analysis indicate that PplD homologs deacetylate the polysaccharide linkage in many streptococcal species. We further demonstrate that introduction of positive charges to the cell wall by GlcNAc deacetylation protects GAS against host cationic antimicrobial proteins.

Original languageEnglish
Article number590
JournalNature Communications
Issue number1
StatePublished - Dec 2022

Bibliographical note

Funding Information:
The authors thank Dr. John F. Timoney (University of Kentucky) for providing S. equi, Dr. Jeffrey M. Bosken, and Dr. Edward D. Hall (University of Kentucky) for the use of the Thermo Fisher Scientific GC-Mass Spectrometer, Dr. Catalina Velez-Ortega (University of Kentucky) for the access to Leica SP8 confocal microscope, and Dr. Peter H. Spielmann (University of Kentucky) for helpful discussions. This work was supported by NIH grants R01 AI143690 from the NIAID and R01 DE028916 from the NIDCR and (to N.K.), the Swedish Research Council (no. 2017-03703) and The Knut and Alice Wal-lenberg Foundation (to G.W.). The Swedish NMR Centre at University of Gothenburg is acknowledged for support. Use of the Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, is supported by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract No. DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research, and by the National Institutes of Health, National Institute of General Medical Sciences (P30GM133894). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Publisher Copyright:
© 2022, The Author(s).

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • General
  • Physics and Astronomy (all)


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