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Structure and metabolism of peptidoglycan and molecular requirements allowing its detection by the Drosophila innate immune system

Institut de Biochimie et Biophysique Moléculaire et Cellulaire, CNRS, Université Paris-Sud, Paris, France, dominique.mengin-lecreulx{at}ebp.u-psud.fr

Bruno Lemaitre

Centre de Génétique Moléculaire, CNRS, Gif-sur-Yvette, France

Peptidoglycan (murein) is a major essential and specific constituent of the bacterial cell wall. Its main function is to protect cells against the internal osmotic pressure and to maintain the characteristic cell shape. It also serves as a platform for the anchoring of specific proteins and other cell wall components. This giant macromolecule is composed of long glycan chains cross-linked by short peptides. Any alteration of the disaccharide—peptide basic unit results in a global change of peptidoglycan structure and properties. Such global variations are encountered in nature as conserved variations along phyletic lines but have sometimes been acquired as a result of mutations or as a mechanism of resistance against cell-wall targeted antibiotics. During bacterial cell growth and division, the peptidoglycan mesh is constantly broken down by a set of highly specific hydrolases in a maturation process allowing insertion of newly synthesized units in the pre-existing polymerized material. Depending on the bacterial species considered, degradation fragments are either released in the growth medium or efficiently re-utilized for synthesis of new murein in a sequence of events termed the recycling pathway. Peptidoglycan is one of the main pathogen-associated molecular patterns recognized by the host innate immune system. Variations of the structure and metabolism of this cell wall component have been exploited by host defense mechanisms for detection/identification of invading bacterial species. Modification of the peptidoglycan structure could also represent a mechanism allowing bacteria to escape these host defense systems.

Key Words: Bacterial cell wall • peptidoglycan • murein • innate immunity • peptidoglycan recognition proteins • antibiotics

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