title: Colicin M, a peptidoglycan lipid-II-degrading enzyme: potential use for antibacterial means?
abstract: Colicins are proteins produced by some strains of Escherichia coli to kill competitors belonging to the same species. Among them, ColM (colicin M) is the only one that blocks the biosynthesis of peptidoglycan, a specific bacterial cell-wall polymer essential for cell integrity. ColM acts in the periplasm by hydrolysing the phosphoester bond of the peptidoglycan lipid intermediate (lipid II). ColM cytotoxicity is dependent on FkpA of the targeted cell, a chaperone with peptidylprolyl cis-trans isomerase activity. Dissection of ColM was used to delineate the catalytic domain and to identify the active-site residues. The in vitro activity of the isolated catalytic domain towards lipid II was 50-fold higher than that of the full-length bacteriocin. Moreover, this domain was bactericidal in the absence of FkpA under conditions that bypass the import mechanism (FhuA-TonB machinery). Thus ColM undergoes a maturation process driven by FkpA that is not required for the activity of the isolated catalytic domain. Genes encoding proteins with similarity to the catalytic domain of ColM were identified in pathogenic strains of Pseudomonas and other genera. ColM acts on several structures of lipid II representative of the diversity of peptidoglycan chemotypes. All together, these data open the way to the potential use of ColM-related bacteriocins as broad spectrum antibacterial agents.
authors.affiliation: Laboratoire des Enveloppes Bactériennes et Antibiotiques, IBBMC, Université Paris-Sud, UMR 8619 CNRS, 91405 Orsay, France. thierry.touze@u-psud.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Touzé
authors.forename: Hélène
authors.initials: H
authors.lastname: Barreteau
authors.forename: Meriem
authors.initials: M
authors.lastname: El Ghachi
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bouhss
authors.forename: Aurélie
authors.initials: A
authors.lastname: Barnéoud-Arnoulet
authors.forename: Delphine
authors.initials: D
authors.lastname: Patin
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Sacco
authors.forename: Didier
authors.initials: D
authors.lastname: Blanot
authors.forename: Michel
authors.initials: M
authors.lastname: Arthur
authors.forename: Denis
authors.initials: D
authors.lastname: Duché
authors.forename: Roland
authors.initials: R
authors.lastname: Lloubès
authors.forename: Dominique
authors.initials: D
authors.lastname: Mengin-Lecreulx
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000898:Antibiosis; D001430:Bacteriocins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D003087:Colicins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D010457:Peptidoglycan / Q000378:metabolism*; D011487:Protein Conformation; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D003087:Colicins; D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol