A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening

BioMed Research International
Lucia CarranoFlavia Marinelli

Abstract

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-dru...Continue Reading

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Citations

Oct 30, 2015·Journal of Natural Products·João C S CruzStefano Donadio
Mar 9, 2017·Microbiology·Karen Machado GomesMaria do Carmo de Freire Bastos

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Methods Mentioned

BETA
Assay

Software Mentioned

MEGA5
Clustal
MEGA
BioNJ
BLASTN
- Omega
BioEdit

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