The Lysozyme-Induced Peptidoglycan N -Acetylglucosamine Deacetylase PgdA (EF1843) Is Required for Enterococcus faecalis Virulence - Université Paris-Est-Créteil-Val-de-Marne Access content directly
Journal Articles Journal of Bacteriology Year : 2012

The Lysozyme-Induced Peptidoglycan N -Acetylglucosamine Deacetylase PgdA (EF1843) Is Required for Enterococcus faecalis Virulence

Abdellah Benachour
  • Function : Author
Rabia Ladjouzi
André Le Jeune
  • Function : Author
Laurent Hébert
  • Function : Author
Simon Thorpe
  • Function : Author
Pascal Courtin
  • Function : Author
Marie-Pierre Chapot-Chartier
Tomasz Prajsnar
  • Function : Author
Simon Foster
  • Function : Author
Stéphane Mesnage
  • Function : Author

Abstract

ABSTRACT Lysozyme is a key component of the innate immune response in humans that provides a first line of defense against microbes. The bactericidal effect of lysozyme relies both on the cell wall lytic activity of this enzyme and on a cationic antimicrobial peptide activity that leads to membrane permeabilization. Among Gram-positive bacteria, the opportunistic pathogen Enterococcus faecalis has been shown to be extremely resistant to lysozyme. This unusual resistance is explained partly by peptidoglycan O -acetylation, which inhibits the enzymatic activity of lysozyme, and partly by d -alanylation of teichoic acids, which is likely to inhibit binding of lysozyme to the bacterial cell wall. Surprisingly, combined mutations abolishing both peptidoglycan O -acetylation and teichoic acid alanylation are not sufficient to confer lysozyme susceptibility. In this work, we identify another mechanism involved in E. faecalis lysozyme resistance. We show that exposure to lysozyme triggers the expression of EF1843, a protein that is not detected under normal growth conditions. Analysis of peptidoglycan structure from strains with EF1843 loss- and gain-of-function mutations, together with in vitro assays using recombinant protein, showed that EF1843 is a peptidoglycan N -acetylglucosamine deacetylase. EF1843-mediated peptidoglycan deacetylation was shown to contribute to lysozyme resistance by inhibiting both lysozyme enzymatic activity and, to a lesser extent, lysozyme cationic antimicrobial activity. Finally, EF1843 mutation was shown to reduce the ability of E. faecalis to cause lethality in the Galleria mellonella infection model. Taken together, our results reveal that peptidoglycan deacetylation is a component of the arsenal that enables E. faecalis to thrive inside mammalian hosts, as both a commensal and a pathogen.

Dates and versions

hal-04322111 , version 1 (04-12-2023)

Identifiers

Cite

Abdellah Benachour, Rabia Ladjouzi, André Le Jeune, Laurent Hébert, Simon Thorpe, et al.. The Lysozyme-Induced Peptidoglycan N -Acetylglucosamine Deacetylase PgdA (EF1843) Is Required for Enterococcus faecalis Virulence. Journal of Bacteriology, 2012, 194 (22), pp.6066-6073. ⟨10.1128/JB.00981-12⟩. ⟨hal-04322111⟩
21 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More