Lichen and Its Microbiome as an Untapped Source of Anti-Biofilm Compounds

Lichen substances have been first described in the 1870s, and around 10 000 compounds have been isolated and characterized. Most of them have been evaluated for their activity on planktonic microorganisms (bacteria and fungi). More recently, microorganisms colonizing the lichen thallus have been isolated and identified using DNA sequencing, giving access to a wide diversity of culturable microorganisms. The increasing research in lichen-associated microbiomes in recent years has emphasized a wide range of metabolites as a potential source of bioactive compounds. In parallel, humans are facing microbial resistance to conventional antimicrobial drugs. One of the reasons is the biofilm lifestyle of microorganisms. Indeed, the aggregation of microbial communities inside biofilms is now well known and characterized, and some possible ways to fight and destroy biofilms are identified (quorum sensing inhibitors, etc.). The present review aims to summarize the anti-biofilm potential of lichen metabolites and those from their associated microorganisms (bacteria and/or fungi). Are the metabolites isolated from lichens and their associated fungi displaying any anti-biofilm activity? This literature synthesis highlights the metabolites of interest as new anti-biofilm drugs and shows the lack of current biological research dealing with biofilm and lichen metabolites. Acetone and ethyl acetate extracts are the most studied sources of anti-biofilm agents. Only two lichen metabolites, usnic acid and evernic acid, have been evaluated both as antifungal and antibacterial biofilm compounds. Terpenoids from lichens are still poorly explored for this activity.