In vitro characterization of the antivirulence target of Gram-positive pathogens, peptidoglycan O-acetyltransferase A (OatA).

PLoS Pathogens
David SychanthaAnthony J Clarke

Abstract

The O-acetylation of the essential cell wall polymer peptidoglycan occurs in most Gram-positive bacterial pathogens, including species of Staphylococcus, Streptococcus and Enterococcus. This modification to peptidoglycan protects these pathogens from the lytic action of the lysozymes of innate immunity systems and, as such, is recognized as a virulence factor. The key enzyme involved, peptidoglycan O-acetyltransferase A (OatA) represents a particular challenge to biochemical study since it is a membrane associated protein whose substrate is the insoluble peptidoglycan cell wall polymer. OatA is predicted to be bimodular, being comprised of an N-terminal integral membrane domain linked to a C-terminal extracytoplasmic domain. We present herein the first biochemical and kinetic characterization of the C-terminal catalytic domain of OatA from two important human pathogens, Staphylococcus aureus and Streptococcus pneumoniae. Using both pseudosubstrates and novel biosynthetically-prepared peptidoglycan polymers, we characterized distinct substrate specificities for the two enzymes. In addition, the high resolution crystal structure of the C-terminal domain reveals an SGNH/GDSL-like hydrolase fold with a catalytic triad of amino acid...Continue Reading

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Citations

Mar 7, 2018·Journal of Molecular Microbiology and Biotechnology·Carlos Eduardo Serrano-MaldonadoMaricarmen Quirasco
Jul 25, 2019·Antimicrobial Agents and Chemotherapy·Amy G PraterYousif Shamoo
Oct 18, 2018·Frontiers in Microbiology·David SychanthaAnthony J Clarke
Sep 7, 2018·Frontiers in Plant Science·Markus Pauly, Vicente Ramírez
Sep 20, 2020·Nature Communications·Timm FiebigMartina Mühlenhoff
Aug 26, 2020·The Journal of Infectious Diseases·Marta Martínez-GuitiánAlejandro Beceiro
Sep 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Carys S JonesAnthony J Clarke

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Methods Mentioned

BETA
amidation
X-ray
transglycosylation
PCR
circular dichroism
protein assay

Software Mentioned

COOT
PHENIX AutoBuild
MCSG Crystallization Suite
HKL2MAP
SOLVE
REFINE
RESOLVE
cealign
TLSMD
Phyre2

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