title: Formicin - a novel broad-spectrum two-component lantibiotic produced by Bacillus paralicheniformis APC 1576.
abstract: Bacteriocins represent a rather underutilized class of antimicrobials despite often displaying activity against many drug-resistant pathogens. Lantibiotics are a post-translationally modified class of bacteriocins, characterized by the presence of lanthionine and methyllanthionine bridges. In this study, a novel two-peptide lantibiotic was isolated and characterized. Formicin was isolated from Bacillus paralicheniformis APC 1576, an antimicrobial-producing strain originally isolated from the intestine of a mackerel. Genome sequencing allowed for the detection of the formicin operon and, from this, the formicin structural genes were identified, along with those involved in lantibiotic modification, transport and immunity. The identified bacteriocin was subsequently purified from the bacterial supernatant. Despite the degree of conservation seen amongst the entire class of two-peptide lantibiotics, the formicin peptides are unique in many respects. The formicin α peptide is far less hydrophobic than any of the equivalent lantibiotics, and with a charge of plus two, it is one of the most positively charged α peptides. The β peptide is unique in that it is the only such peptide with a negative charge due to the presence of an aspartic acid residue in the C-terminus, possibly indicating a slight variation to the mode of action of the bacteriocin. Formicin also displays a broad spectrum of inhibition against Gram-positive strains, inhibiting many clinically relevant pathogens such as Staphylococcus aureus, Clostridium difficile and Listeria monocytogenes. The range of inhibition displayed against many important pathogens indicates a potential therapeutic use against such strains where antibiotic resistance is such a growing concern.
authors.affiliation: Teagasc Food Research Centre, Teagasc Moorepark, Fermoy, Cork, Ireland.|APC Microbiome Institute, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Fergus W J
authors.initials: FWJ
authors.lastname: Collins
authors.affiliation: Teagasc Food Research Centre, Teagasc Moorepark, Fermoy, Cork, Ireland.|APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: Paula M
authors.initials: PM
authors.lastname: O'Connor
authors.affiliation: Teagasc Food Research Centre, Teagasc Moorepark, Fermoy, Cork, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: O'Sullivan
authors.affiliation: Teagasc Food Research Centre, Teagasc Moorepark, Fermoy, Cork, Ireland.|APC Microbiome Institute, University College Cork, Cork, Ireland.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Rea
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|Department of Microbiology, University College Cork, Cork, Ireland.
authors.forename: Colin
authors.initials: C
authors.lastname: Hill
authors.affiliation: APC Microbiome Institute, University College Cork, Cork, Ireland.|Teagasc Food Research Centre, Teagasc Moorepark, Fermoy, Cork, Ireland.|College of Science Engineering and Food Science, University College Cork, Cork, Ireland.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Ross
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D001407:Bacillus / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001430:Bacteriocins / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000187:drug effects; D008969:Molecular Sequence Data; D010473:Perciformes / Q000382:microbiology; D016415:Sequence Alignment; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins