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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 anaerob...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539421/ https://www.ncbi.nlm.nih.gov/pubmed/26346738 http://dx.doi.org/10.1155/2015/419383 |
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author | Carrano, Lucia Abbondi, Monica Turconi, Paola Candiani, Gianpaolo Marinelli, Flavia |
author_facet | Carrano, Lucia Abbondi, Monica Turconi, Paola Candiani, Gianpaolo Marinelli, Flavia |
author_sort | Carrano, Lucia |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4539421 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-45394212015-09-06 A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening Carrano, Lucia Abbondi, Monica Turconi, Paola Candiani, Gianpaolo Marinelli, Flavia Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2015 2015-08-04 /pmc/articles/PMC4539421/ /pubmed/26346738 http://dx.doi.org/10.1155/2015/419383 Text en Copyright © 2015 Lucia Carrano et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Carrano, Lucia Abbondi, Monica Turconi, Paola Candiani, Gianpaolo Marinelli, Flavia A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening |
title | A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening |
title_full | A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening |
title_fullStr | A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening |
title_full_unstemmed | A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening |
title_short | A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening |
title_sort | novel microbisporicin producer identified by early dereplication during lantibiotic screening |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539421/ https://www.ncbi.nlm.nih.gov/pubmed/26346738 http://dx.doi.org/10.1155/2015/419383 |
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