De-O-acetylation of peptidoglycan regulates glycan chain extension and affects in vivo survival of Neisseria meningitidis

Authors

  • Frédéric J. Veyrier,

    Corresponding author
    1. Institut Pasteur, Groupe Biologie et Génétique de la Paroi Bactérienne, Département de Microbiologie, Paris, France
    2. INSERM, Groupe Avenir, Paris, France
    • Institut Pasteur, Infections Bactériennes Invasives, Département Infection et Epidémiologie, Paris, France
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  • Allison H. Williams,

    1. Institut Pasteur, Groupe Biologie et Génétique de la Paroi Bactérienne, Département de Microbiologie, Paris, France
    2. INSERM, Groupe Avenir, Paris, France
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  • Stéphane Mesnage,

    1. Centre de Recherches des Cordeliers, Inserm U872, Paris, France
    Current affiliation:
    1. Krebs Institute, University of Sheffield, Sheffield, UK
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  • Christine Schmitt,

    1. Institut Pasteur, Plate-forme de Microscopie Ultrastructurale, Département de Biologie Cellulaire et Infection, Paris, France
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  • Muhamed-Kheir Taha,

    1. Institut Pasteur, Infections Bactériennes Invasives, Département Infection et Epidémiologie, Paris, France
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  • Ivo G. Boneca

    Corresponding author
    1. Institut Pasteur, Groupe Biologie et Génétique de la Paroi Bactérienne, Département de Microbiologie, Paris, France
    2. INSERM, Groupe Avenir, Paris, France
    • Institut Pasteur, Infections Bactériennes Invasives, Département Infection et Epidémiologie, Paris, France
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For correspondence. E-mail frederic.veyrier@pasteur.fr; Tel. (+33) 1 4061 3883; Fax (+33) 1 4061 3034; E-mail bonecai@pasteur.fr; Tel. (+33) 1 4438 9516; Fax (+33) 1 4061 3640.

Summary

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.

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