Discovery of Biofilm Inhibitors from the Microbiota of Marine Egg Masses

Biofilms commonly develop in immunocompromised patients, which leads to persistent infections that are difficult to treat. In the biofilm state, bacteria are protected against both antibiotics and the host’s immune system; currently, there are no therapeutics that target biofilms. In this study, we screened a chemical fraction library representing the natural product capacity of the microbiota of marine egg masses, namely, the moon snail egg collars. This led to the identification of active fractions targeting both Pseudomonas aeruginosa and Staphylococcus aureus biofilms. Subsequent analysis revealed that a subset of these fractions were capable of eradicating pre-formed biofilms, all against S. aureus. Bioassay-guided isolations led to identifying pseudochelin A, a known siderophore, as a S. aureus biofilm inhibitor with an IC50 of 34.1 μg/mL. Mass spectrometry-based metabolomic analyses revealed widespread production of pseudochelin A among fractions possessing S. aureus antibiofilm properties. In addition, a key biosynthetic gene involved in producing pseudochelin A was detected on 30% of the moon snail egg collars and pseudochelin A is capable of inhibiting the formation of biofilms (IC50 19.5 μg/mL) produced by ecologically relevant bacterial strains. All suggesting that pseudochelin A may have a role in shaping the microbiome or protecting the egg collars from microbiofouling.