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De-O-acetylation of peptidoglycan regulates glycan chain extension and affects in vivo survival of Neisseria meningitidis.
MedLine Citation:
PMID:  23373517     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Peptidoglycan O-acetylation is a modification found in many bacteria. In Gram-positive pathogens, it contributes to virulence by conferring resistance to host lysozyme. However, in Gram-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 Neisseria meningitidis (Nm). Using genetic expression of all possible combinations of the three genes in Escherichia 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.
Authors:
Frédéric J Veyrier; Allison H Williams; Stéphane Mesnage; Christine Schmitt; Muhamed-Kheir Taha; Ivo G Boneca
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-3
Journal Detail:
Title:  Molecular microbiology     Volume:  -     ISSN:  1365-2958     ISO Abbreviation:  Mol. Microbiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712028     Medline TA:  Mol Microbiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 Blackwell Publishing Ltd.
Affiliation:
Institut Pasteur, Infections Bactériennes Invasives, Département Infection et Epidémiologie, 28 Rue du Dr. Roux, Paris, F-75015, France; Institut Pasteur, Groupe Biologie et Génétique de la Paroi Bactérienne, Département de Microbiologie, 28 Rue du Dr. Roux, Paris, F-75015, France; INSERM, Groupe Avenir, Paris, F-75015, France.
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