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De‐ O ‐acetylation of peptidoglycan regulates glycan chain extension and affects in vivo survival of N eisseria meningitidis
Author(s) -
Veyrier Frédéric J.,
Williams Allison H.,
Mesnage Stéphane,
Schmitt Christine,
Taha MuhamedKheir,
Boneca Ivo G.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12153
Subject(s) - acetylation , biology , peptidoglycan , glycan , virulence , microbiology and biotechnology , lysozyme , operon , biochemistry , cell wall , escherichia coli , gene , glycoprotein
Summary Peptidoglycan O ‐acetylation is a modification found in many bacteria. In G ram‐positive pathogens, it contributes to virulence by conferring resistance to host lysozyme. However, in G ram‐negative pathogens, its contribution to physiology and virulence is unknown. We examined the contribution of patA , patB and ape1 to peptidoglycan O ‐acetylation in the major human pathogen N eisseria meningitidis ( Nm ). Using genetic expression of all possible combinations of the three genes in E scherichia coli and Nm , we confirmed that PatA and PatB were required for PG O ‐acetylation, while ApeI removed the O ‐acetyl group. ApeI was active on all O ‐acetylated muropeptides produced by PatA and PatB during heterologous expression in E . coli and was also active on several PG structures in vitro . Interestingly, in Nm , ApeI was found to preferentially de‐ O ‐acetylate muropeptides with tripeptide stems ( GM3 ), suggesting that its activity is highly regulated. Accordingly, de‐ O ‐acetylation of GM3 regulated glycan chain elongation and cell size. Additionally, the virulence of Nm lacking ApeI was drastically reduced suggesting that regulation of glycan chain length by O ‐acetylation contributes to bacterial fitness in the host. Altogether, our results suggest that ApeI represents an attractive target for new drug development.