Bioactive Compounds Produced by Hypoxylon fragiforme against Staphylococcus aureus Biofilms

Area of Science:

• Mycology
• Microbiology
• Natural Product Chemistry

Background:

• Biofilm infections pose a significant challenge due to pathogen resistance to antibiotics and immune responses.
• Fungi, often thriving in moist environments conducive to bacterial biofilm growth, may possess mechanisms to regulate these biofilms.

Purpose of the Study:

• To investigate the potential of the fungus Hypoxylon fragiforme to produce compounds that inhibit bacterial biofilm formation.
• To identify and characterize novel bioactive compounds from H. fragiforme with anti-biofilm activity.

Main Methods:

• Cultivation and fermentation of Hypoxylon fragiforme.
• Extraction and isolation of secondary metabolites.
• In vitro testing of isolated compounds against Staphylococcus aureus biofilm formation and pre-formed biofilms.
• Determination of compound activity and specificity.

Main Results:

• Sclerin and sclerin diacid were isolated from H. fragiforme for the first time.
• Sclerin and sclerin diacid inhibited Staphylococcus aureus biofilm formation by 86% and 80% at 256 μg mL⁻¹, respectively, without killing the bacteria.
• The monomethylester of sclerin diacid showed no activity.
• Compounds were effective at subtoxic concentrations and prevented biofilm formation but not mature biofilms.
• Sclerin and sclerin diacid demonstrated high specificity against S. aureus.

Conclusions:

• Hypoxylon fragiforme produces sclerin and sclerin diacid with potent anti-biofilm formation activity against Staphylococcus aureus.
• These compounds represent a promising natural strategy for controlling pathogenic biofilms, potentially enhancing antibiotic efficacy through combination therapy.