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.
Highlights
Bacterial biofilms is the term used to describe the surface-attached bacterial lifestyle
S. aureus is a very versatile pathogen due to its various resistance mechanisms and it is frequently associated to hospital-acquired infections, which are often related to biofilms in medical devices [15,16,17]
Furanones, a naturally occurring class of compounds, have shown ability to prevent bacterial adhesion, which could be related to some extent to their inhibitory effects of quorum sensing in Staphylococcus spp
Summary
Bacterial biofilms is the term used to describe the surface-attached bacterial lifestyle. We attempted to find and characterize compounds acting on S. aureus biofilms from a collection of abietane-type diterpenes containing relatively simple resin acids that have not been previously studied. These compounds are available, chemically stable and cost-effective which altogether benefit their wider exploitation as potent anti-biofilm probes in laboratory trials. Focusing on these compounds allows the revalorization of a previously neglected product from the forest industry (wood rosin), which is a desirable strategy towards the discovery of more environmentally friendly biocides
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