title: Relatedness between the two-component lantibiotics lacticin 3147 and staphylococcin C55 based on structure, genetics and biological activity.
abstract: BACKGROUND
  Two component lantibiotics, such as the plasmid-encoded lacticin 3147 produced by Lactococcus lactis DPC3147 and staphylococcin C55 produced by Staphylococcus aureus C55, represent an emerging subgroup of bacteriocins. These two bacteriocins are particularly closely related, exhibiting 86% (LtnA1 and C55alpha) and 55% (LtnA2 and C55beta) identity in their component peptides. The aim of this study was to investigate, for the first time for any two component bacteriocins, the significance of the relatedness between these two systems.
  
  
  RESULTS
  So close is this relatedness that the hybrid peptide pairs LtnA1:C55beta and C55alpha:LtnA2 were found to have activities in the single nanomolar range, comparing well with the native pairings. To determine whether this flexibility extended to the associated post-translational modification/processing machinery, the staphylococcin C55 structural genes were directly substituted for their lacticin 3147 counterparts in the ltn operon on the large conjugative lactococcal plasmid pMRC01. It was established that the lacticin LtnA1 post-translational and processing machinery could produce functionally active C55alpha, but not C55beta. In order to investigate in closer detail the significance of the differences between LtnA1 and C55alpha, three residues in LtnA1 were replaced with the equivalent residues in C55alpha. Surprisingly, one such mutant LtnA1-Leu21Ala was not produced. This may be significant given the positioning of this residue in a putative lipid II binding loop.
  
  
  CONCLUSIONS
  It is apparent, despite sharing striking similarities in terms of structure and activity, that these two complex bacteriocins display some highly dedicated features particular to either system.
authors.affiliation: Moorepark Food Research Centre, Teagasc, Fermoy, Co., Cork, Ireland. eileen.oconnor@teagasc.ie <eileen.oconnor@teagasc.ie>
authors.forename: Eileen B
authors.initials: EB
authors.lastname: O'Connor
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cotter
authors.forename: Paula
authors.initials: P
authors.lastname: O'Connor
authors.forename: Orla
authors.initials: O
authors.lastname: O'Sullivan
authors.forename: John R
authors.initials: JR
authors.lastname: Tagg
authors.forename: R Paul
authors.initials: RP
authors.lastname: Ross
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use*; D001430:Bacteriocins / Q000737:chemistry / Q000235:genetics* / Q000627:therapeutic use*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D014644:Genetic Variation; D013294:Lactococcus lactis / Q000235:genetics; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry; D013211:Staphylococcus aureus / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010455:Peptides; C082508:lacticin 481; C017724:staphylococcin