TY - JOUR
T1 - PplD is a de-N-acetylase of the cell wall linkage unit of streptococcal rhamnopolysaccharides
AU - Rush, Jeffrey S
AU - Parajuli, Prakash
AU - Ruda, Alessandro
AU - Li, Jian
AU - Pohane, Amol Arunrao
AU - Zamakhaeva, Svetlana
AU - Rahman, Mohammad M
AU - Chang, Jennifer C
AU - Gogos, Artemis
AU - Kenner, Cameron W
AU - Lambeau, Gérard
AU - Federle, Michael J
AU - Korotkov, Konstantin V
AU - Widmalm, Göran
AU - Korotkova, Natalia
N1 - © 2022. The Author(s).
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-28257-0
DO - 10.1038/s41467-022-28257-0
M3 - Article
C2 - 35105886
SN - 2041-1723
VL - 13
SP - 590
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -
