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

Nat Commun. 2022 Feb 1;13(1):590. doi: 10.1038/s41467-022-28257-0.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylesterase / metabolism*
  • Acetylglucosamine / metabolism
  • Bacterial Proteins / metabolism
  • Cell Wall / metabolism*
  • Crystallography, X-Ray
  • Glucosamine / analogs & derivatives
  • Glucosephosphates
  • Histones
  • Humans
  • Nitrous Acid
  • Peptidoglycan / chemistry
  • Peptidoglycan / metabolism
  • Polysaccharides, Bacterial / metabolism*
  • Streptococcal Infections / microbiology
  • Streptococcus / metabolism*
  • Streptococcus mutans

Substances

  • Bacterial Proteins
  • Glucosephosphates
  • Histones
  • Peptidoglycan
  • Polysaccharides, Bacterial
  • glucosamine 1-phosphate
  • Acetylesterase
  • Glucosamine
  • Nitrous Acid
  • Acetylglucosamine