(+)-Dehydroabietic acid, an abietane-type diterpene, inhibits Staphylococcus aureus biofilms in vitro

Adyary Fallarero, Malena Skogman, Janni Kujala, Mohanathas Rajaratnam, Vânia M. Moreira, Jari Yli-Kauhaluoma, Pia Vuorela

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed at exploring biofilms behavior and functionability. In this contribution, a collection of naturally-occurring abietane-type diterpenes and their derivatives was tested against S. aureus biofilms using a platform consisting of two phenotypic assays that have been previously published by our group. Three active compounds were identified: nordehydroabietylamine (1), (+)-dehydroabietic acid (2) and (+)-dehydroabietylamine (3) that prevented biofilm formation in the low micromolar range, and unlike typical antibiotics, only 2 to 4-fold higher concentrations were needed to significantly reduce viability and biomass of existing biofilms. Compound 2, (+)-dehydroabietic acid, was the most selective towards biofilm bacteria, achieving high killing efficacy (based on log Reduction values) and it was best tolerated by three different mammalian cell lines. Since (+)-dehydroabietic acid is an easily available compound, it holds great potential to be used as a molecular probe in biofilms-related studies as well as to serve as inspirational chemical model for the development of potent drug candidates.

LanguageEnglish
Pages12054-12072
Number of pages19
JournalInternational Journal of Molecular Sciences
Volume14
Issue number6
DOIs
Publication statusPublished - 5 Jun 2013

Fingerprint

Abietane Diterpenes
biofilms
staphylococcus
Biofilms
Staphylococcus aureus
acids
Acids
drugs
Chemical Models
Molecular Probes
In Vitro Techniques
dehydroabietic acid
antibiotics
infectious diseases
Antibiotics
biomass
organisms
cultured cells
Bacterial Infections
viability

Keywords

  • biofilm infections
  • anti-bacterial agents
  • biocompatible materials
  • Staphylococcus aureus

Cite this

Fallarero, Adyary ; Skogman, Malena ; Kujala, Janni ; Rajaratnam, Mohanathas ; Moreira, Vânia M. ; Yli-Kauhaluoma, Jari ; Vuorela, Pia. / (+)-Dehydroabietic acid, an abietane-type diterpene, inhibits Staphylococcus aureus biofilms in vitro. In: International Journal of Molecular Sciences. 2013 ; Vol. 14, No. 6. pp. 12054-12072.
@article{aeb4506d858f4399a847527cda0b1e8e,
title = "(+)-Dehydroabietic acid, an abietane-type diterpene, inhibits Staphylococcus aureus biofilms in vitro",
abstract = "Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed at exploring biofilms behavior and functionability. In this contribution, a collection of naturally-occurring abietane-type diterpenes and their derivatives was tested against S. aureus biofilms using a platform consisting of two phenotypic assays that have been previously published by our group. Three active compounds were identified: nordehydroabietylamine (1), (+)-dehydroabietic acid (2) and (+)-dehydroabietylamine (3) that prevented biofilm formation in the low micromolar range, and unlike typical antibiotics, only 2 to 4-fold higher concentrations were needed to significantly reduce viability and biomass of existing biofilms. Compound 2, (+)-dehydroabietic acid, was the most selective towards biofilm bacteria, achieving high killing efficacy (based on log Reduction values) and it was best tolerated by three different mammalian cell lines. Since (+)-dehydroabietic acid is an easily available compound, it holds great potential to be used as a molecular probe in biofilms-related studies as well as to serve as inspirational chemical model for the development of potent drug candidates.",
keywords = "biofilm infections, anti-bacterial agents, biocompatible materials, Staphylococcus aureus",
author = "Adyary Fallarero and Malena Skogman and Janni Kujala and Mohanathas Rajaratnam and Moreira, {V{\^a}nia M.} and Jari Yli-Kauhaluoma and Pia Vuorela",
year = "2013",
month = "6",
day = "5",
doi = "10.3390/ijms140612054",
language = "English",
volume = "14",
pages = "12054--12072",
journal = "International Journal of Molecular Sciences",
issn = "1422-0067",
number = "6",

}

(+)-Dehydroabietic acid, an abietane-type diterpene, inhibits Staphylococcus aureus biofilms in vitro. / Fallarero, Adyary; Skogman, Malena; Kujala, Janni; Rajaratnam, Mohanathas; Moreira, Vânia M.; Yli-Kauhaluoma, Jari; Vuorela, Pia.

In: International Journal of Molecular Sciences, Vol. 14, No. 6, 05.06.2013, p. 12054-12072.

Research output: Contribution to journalArticle

TY - JOUR

T1 - (+)-Dehydroabietic acid, an abietane-type diterpene, inhibits Staphylococcus aureus biofilms in vitro

AU - Fallarero, Adyary

AU - Skogman, Malena

AU - Kujala, Janni

AU - Rajaratnam, Mohanathas

AU - Moreira, Vânia M.

AU - Yli-Kauhaluoma, Jari

AU - Vuorela, Pia

PY - 2013/6/5

Y1 - 2013/6/5

N2 - Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed at exploring biofilms behavior and functionability. In this contribution, a collection of naturally-occurring abietane-type diterpenes and their derivatives was tested against S. aureus biofilms using a platform consisting of two phenotypic assays that have been previously published by our group. Three active compounds were identified: nordehydroabietylamine (1), (+)-dehydroabietic acid (2) and (+)-dehydroabietylamine (3) that prevented biofilm formation in the low micromolar range, and unlike typical antibiotics, only 2 to 4-fold higher concentrations were needed to significantly reduce viability and biomass of existing biofilms. Compound 2, (+)-dehydroabietic acid, was the most selective towards biofilm bacteria, achieving high killing efficacy (based on log Reduction values) and it was best tolerated by three different mammalian cell lines. Since (+)-dehydroabietic acid is an easily available compound, it holds great potential to be used as a molecular probe in biofilms-related studies as well as to serve as inspirational chemical model for the development of potent drug candidates.

AB - Potent drugs are desperately needed to counteract bacterial biofilm infections, especially those caused by gram-positive organisms, such as Staphylococcus aureus. Moreover, anti-biofilm compounds/agents that can be used as chemical tools are also needed for basic in vitro or in vivo studies aimed at exploring biofilms behavior and functionability. In this contribution, a collection of naturally-occurring abietane-type diterpenes and their derivatives was tested against S. aureus biofilms using a platform consisting of two phenotypic assays that have been previously published by our group. Three active compounds were identified: nordehydroabietylamine (1), (+)-dehydroabietic acid (2) and (+)-dehydroabietylamine (3) that prevented biofilm formation in the low micromolar range, and unlike typical antibiotics, only 2 to 4-fold higher concentrations were needed to significantly reduce viability and biomass of existing biofilms. Compound 2, (+)-dehydroabietic acid, was the most selective towards biofilm bacteria, achieving high killing efficacy (based on log Reduction values) and it was best tolerated by three different mammalian cell lines. Since (+)-dehydroabietic acid is an easily available compound, it holds great potential to be used as a molecular probe in biofilms-related studies as well as to serve as inspirational chemical model for the development of potent drug candidates.

KW - biofilm infections

KW - anti-bacterial agents

KW - biocompatible materials

KW - Staphylococcus aureus

UR - http://www.mdpi.com/1422-0067/14/6/12054

U2 - 10.3390/ijms140612054

DO - 10.3390/ijms140612054

M3 - Article

VL - 14

SP - 12054

EP - 12072

JO - International Journal of Molecular Sciences

T2 - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 6

ER -