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A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening.

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 ?-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 ?-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.

SUBMITTER: Carrano L

PROVIDER: S-EPMC4539421 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening.

Carrano Lucia L Abbondi Monica M Turconi Paola P Candiani Gianpaolo G Marinelli Flavia F

BioMed research international 20150804

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 biosynth ...[more]

PMID: 26346738

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Project description:BackgroundFrequent use of antibiotics has led to the emergence of antibiotic resistance in bacteria. Lantibiotic compounds are ribosomally synthesized antimicrobial peptides against which bacteria are not able to produce resistance, hence making them a good alternative to antibiotics. Nisin is the oldest and the most widely used lantibiotic, in food preservation, without having developed any significant resistance against it. Having their antimicrobial potential and a limited number, there is a need to identify novel lantibiotics.Methodology/findingsIdentification of novel lantibiotic biosynthetic clusters from an ever increasing database of bacterial genomes, can provide a major lead in this direction. In order to achieve this, a strategy was adopted to identify novel lantibiotic biosynthetic clusters by screening the sequenced genomes for LanT homolog, which is a conserved lantibiotic transporter specific to type IB clusters. This strategy resulted in identification of 54 bacterial strains containing the LanT homologs, which are not the known lantibiotic producers. Of these, 24 strains were subjected to a detailed bioinformatic analysis to identify genes encoding for precursor peptides, modification enzyme, immunity and quorum sensing proteins. Eight clusters having two LanM determinants, similar to haloduracin and lichenicidin were identified, along with 13 clusters having a single LanM determinant as in mersacidin biosynthetic cluster. Besides these, orphan LanT homologs were also identified which might be associated with novel bacteriocins, encoded somewhere else in the genome. Three identified gene clusters had a C39 domain containing LanT transporter, associated with the LanBC proteins and double glycine type precursor peptides, the only known example of such a cluster is that of salivaricin.ConclusionThis study led to the identification of 8 novel putative two-component lantibiotic clusters along with 13 having a single LanM and 3 with LanBC genes. Putative lantibiotic clusters identified here hold the potential for the discovery of novel lantibiotic(s).

Dataset Information

A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening.

Publications

A Novel Microbisporicin Producer Identified by Early Dereplication during Lantibiotic Screening.

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