Discovery of novel natural anti-biofilm compounds of wide chemical diversity
Lindstedt, Bianca (2021)
Lindstedt, Bianca
2021
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi-fe2021061537549
https://urn.fi/URN:NBN:fi-fe2021061537549
Tiivistelmä
Microorganisms have the tendency to switch from planktonic stage to biofilm and back again depending on the environmental conditions. Microorganisms can attach to all kind of materials and form biofilms. A biofilm develops when microorganisms irreversibly attach to a surface and start producing extracellular polymers. The polymers provide a matrix around the bacteria which protects the microorganisms from environmental factors. A significant part of human bacterial infections is caused by biofilms. Bacterial biofilm infections include lung infections of cystic fibrosis patients, ear infections, wound infections, bacterial endocarditis and infections associated with indwelling medical devices. Biofilms are known to be very resistant to antibiotics and place a significant burden on healthcare system worldwide. Staphylococcus aureus is a gram-positive bacterium that has an ability to adhere to surfaces and form biofilms. The antibiotics on the market today are not effective enough against S. aureus biofilm-related infections. Furthermore, natural products have since long been used to treat different kind of bacterial infections. The chemical diversity they possess, makes them important in the discovery of lead compounds.
The aim of this work was to identify novel natural compounds with anti-biofilm properties, acting on biofilms formed by Staphylococcus aureus. A commercially available Enzo Product Library consisting of 502 natural and naturally derived compounds were at first screened at approximately 40 µM (ranging from 9.4 µM to 130.6 µM), using two S. aureus bacterial strains. Bacteria were exposed to the compounds both prior-to and post-biofilm formation. The viable bacterial mass formed in both assay modes was quantified using resazurin staining, a method previously developed in the laboratory. The workflow was a multistep process. First, twenty compounds were found to inhibit biofilm formation over the activity threshold in both prior-to and/or post-exposure tests in at least one of the tested strains. Second, eight compounds from the primary screening were further considered as most selective based on literature searches, as well as retested in a reconfirmation trial. Finally, four compounds, cromomycin A3, mithramycin A, mitomycin C and minocycline were identified as possible anti-biofilm agents due to their activity on both planktonic and biofilm bacteria. Furthermore, the anti-biofilm potencies of all four compounds were high, which makes them good antimicrobials.
The aim of this work was to identify novel natural compounds with anti-biofilm properties, acting on biofilms formed by Staphylococcus aureus. A commercially available Enzo Product Library consisting of 502 natural and naturally derived compounds were at first screened at approximately 40 µM (ranging from 9.4 µM to 130.6 µM), using two S. aureus bacterial strains. Bacteria were exposed to the compounds both prior-to and post-biofilm formation. The viable bacterial mass formed in both assay modes was quantified using resazurin staining, a method previously developed in the laboratory. The workflow was a multistep process. First, twenty compounds were found to inhibit biofilm formation over the activity threshold in both prior-to and/or post-exposure tests in at least one of the tested strains. Second, eight compounds from the primary screening were further considered as most selective based on literature searches, as well as retested in a reconfirmation trial. Finally, four compounds, cromomycin A3, mithramycin A, mitomycin C and minocycline were identified as possible anti-biofilm agents due to their activity on both planktonic and biofilm bacteria. Furthermore, the anti-biofilm potencies of all four compounds were high, which makes them good antimicrobials.
Kokoelmat
- 317 Farmasia [18]