title: Insights into the mode of action of the two-peptide lantibiotic haloduracin.
abstract: Haloduracin, a recently discovered two-peptide lantibiotic composed of the post-translationally modified peptides Halalpha and Halbeta, is shown to have high potency against a range of Gram-positive bacteria and to inhibit spore outgrowth of Bacillus anthracis. The two peptides display optimal activity in a 1:1 stoichiometry and have efficacy similar to that of the commercially used lantibiotic nisin. However, haloduracin is more stable at pH 7 than nisin. Despite significant structural differences between the two peptides of haloduracin and those of the two-peptide lantibiotic lacticin 3147, these two systems show similarities in their mode of action. Like Ltnalpha, Halalpha binds to a target on the surface of Gram-positive bacteria, and like Ltnbeta, the addition of Halbeta results in pore formation and potassium efflux. Using Halalpha mutants, its B- and C-thioether rings are shown to be important but not required for bioactivity. A similar observation was made with mutants of Glu22, a residue that is highly conserved among several lipid II-binding lantibiotics such as mersacidin.
authors.affiliation: Department of Chemistry, University of Illinois at Urbana-Champaign and the Howard Hughes Medical Institute, Urbana, Illinois 61801, USA.
authors.forename: Trent J
authors.initials: TJ
authors.lastname: Oman
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: van der Donk
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001407:Bacillus / Q000378:metabolism*; D001430:Bacteriocins / Q000235:genetics / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D009561:Nisin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C515824:haloduracin, Bacillus halodurans; D009561:Nisin
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