A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening.
With the increasing need of effective antibiotics against multi-drug resistant pathogens, lantibiotics are an attractive option of a new class of molecules. They are ribosomally synthetized and posttranslationally modified peptides possessing potent antimicrobial activity against aerobic and anaerobic Gram-positive pathogens, including those increasingly resistant to β-lactams and glycopeptides. Some of them (actagardine, mersacidin, planosporicin, and microbisporicin) inhibit cell wall biosynthesis in pathogens and their effect is not antagonized by vancomycin. Hereby, we apply an efficient strategy for lantibiotic screening to 240 members of a newly described genus of filamentous actinomycetes, named Actinoallomurus, that is considered a yet-poorly-exploited promising source for novel bioactive metabolites. By combining antimicrobial differential assay against Staphylococcus aureus and its L-form (also in the presence of a β-lactamase cocktail or Ac-Lys-D-alanyl-D-alanine tripeptide), with LC-UV-MS dereplication coupled with bioautography, a novel producer of the potent microbisporicin complex was rapidly identified. Under the commercial name of NAI-107, it is currently in late preclinical phase for the treatment of multi-drug resistant Gram-positive pathogens. To our knowledge, this is the first report on a lantibiotic produced by an Actinoallomurus sp. and on a microbisporicin producer not belonging to the Microbispora genus.
Fondazione Istituto Insubrico Ricerca per la Vita (F.I.I.R.V.), Via R. Lepetit 32, 21100 Gerenzano, Italy.
Lucia
L
Carrano
Fondazione Istituto Insubrico Ricerca per la Vita (F.I.I.R.V.), Via R. Lepetit 32, 21100 Gerenzano, Italy.
Monica
M
Abbondi
Fondazione Istituto Insubrico Ricerca per la Vita (F.I.I.R.V.), Via R. Lepetit 32, 21100 Gerenzano, Italy.
Paola
P
Turconi
Fondazione Istituto Insubrico Ricerca per la Vita (F.I.I.R.V.), Via R. Lepetit 32, 21100 Gerenzano, Italy.
Gianpaolo
G
Candiani
Dipartimento di Biotecnologie e Scienze della Vita, Università degli Studi dell'Insubria, Via J. H. Dunant 3, 21100 Varese, Italy ; "The Protein Factory" Research Center, Politecnico of Milano, ICRM CNR Milano and University of Insubria, Via J. H. Dunant 3, 21100 Varese, Italy.
Flavia
F
Marinelli
D039903:Actinobacteria / Q000378:metabolism*; D001430:Bacteriocins / Q000096:biosynthesis / Q000494:pharmacology; D002176:Candida albicans / Q000254:growth & development; D013211:Staphylococcus aureus / Q000254:growth & development*
D001430:Bacteriocins; C528150:microbisporicin