Effective antibiofilm polyketides against Staphylococcus aureus from the pyranonaphthoquinone biosynthetic pathways of Streptomyces species.

Terhi Oja, Paola San-Martin-Galindo, Takaaki Taguchi, Suvi Manner, Pia M. Vuorela, Koji Ichinose, Mikko Metsä-Ketelä, Adyary Fallarero

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

Streptomyces bacteria are renowned for their ability to produce bioactive secondary metabolites. Recently, synthetic biology has enabled the production of intermediates and shunt products, which may have altered biological activities in comparison to the end products of the pathways. Here we have evaluated the potential of recently isolated alnumycins and other closely related pyranonaphthoquinone (PNQ) polyketides against Staphylococcus aureus biofilms. The antimicrobial potency of the compounds against planktonic cells and biofilms was determined by redox dye-based viability staining, and the anti-biofilm efficacy of the compounds was confirmed by viable counting. A novel antistaphylococcal polyketide, alnumycin D, was identified. Unexpectedly, the C-ribosylated pathway shunt product alnumycin D was more active against both planktonic and biofilm cells than the pathway end product alnumycin A, where a ribose unit has been converted into a dioxane moiety. The evaluation of the anti-biofilm potential of other alnumycins revealed that the presence of the ribose moiety in pyranose form is essential for high activity against pre-formed biofilms. Furthermore, the anti-biofilm potential of other closely related PNQ polyketides was examined. Based on their previously reported activity against planktonic S. aureus cells, granaticin B, kalafungin and medermycin were also selected for testing here, and among them, granaticin B was found to be the most potent against pre-formed biofilms.The most active anti-biofilm PNQs alnumycin D and granaticin B share several structural features that may be important for the anti-biofilm activity. They are uncharged, glycosylated, and also contain a similar oxygenation pattern of the lateral naphthoquinone ring. The findings highlight the potential of antibiotic biosynthetic pathways as a source of effective anti-biofilm compounds.
Alkuperäiskielienglanti
LehtiAntimicrobial Agents and Chemotherapy
Vuosikerta59
Numero10
Sivut6046-6052
Sivumäärä7
ISSN0066-4804
DOI - pysyväislinkit
TilaJulkaistu - 2015
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 317 Farmasia

Siteeraa tätä