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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.

SUBMITTER: Oman TJ

PROVIDER: S-EPMC2812937 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Insights into the mode of action of the two-peptide lantibiotic haloduracin.

Oman Trent J TJ van der Donk Wilfred A WA

ACS chemical biology 20091001 10

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 differen ...[more]

PMID: 19678697

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Insights into the mode of action of the two-peptide lantibiotic haloduracin.

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Insights into the mode of action of the two-peptide lantibiotic haloduracin.

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