# Lichens as a Natural Source of Compounds Active on Microorganisms of Human Health Interest
## 1 Introduction  
In recent years, a strong interest has been observed in achieving the characterization of biologically active compounds from natural sources especially for their potential therapeutic use in infectious diseases, including fungal infections that can have important consequences in immunocompromised patients [1]. Some sources of biodiversity that may be largely explored are lichens [2]. Lichens can grow on a wide variety of substrates, and they are adapted to survive at any latitude and longitude, in various extreme and adverse environments. Lichens are a well-known symbiotic association of two organisms functioning as a single entity, derived from the close partnership between fungi and algae and/or cyanobacteria [3, 4]. This association allows the lichen to obtain simple sugars, which the algae and/or cyanobacteria transfer to the fungus through photosynthesis, thereby becoming able to biosynthesize complex and specific metabolites [5]. The production of a wide range of primary (intracellular) and secondary (extracellular) compounds gives the lichen much of its intrinsic resistance [6]. Furthermore, lichens produce a wide variety of secondary metabolites that belong to low molecular weight aliphatic and aromatic chemicals that accumulate mainly in the outer cortex or medullary layer [7, 8]. Various compounds have been identified, such as monoaromatics, despides, deposidones, pulvinates, dibenzofurans,anthraquinones, and xanthones [9; 10]. Lichens are still poorly understood as a source of biological compounds, and their potential needs to be fully explored and utilized as they could represent a promising source of bioactive natural products capable of sustaining human life. Some of these substances, similarly to other plants or plant derivatives, exhibit various biological activities to potentially use them in the pharmaceutical field [11; 12; 13; 14]. Antimicrobial activity is frequently found in lichens that produce compounds such as atranorin, salazinic acid, licanoric acid, and usnic acid, with both antibacterial and antifungal properties against microorganisms of interest in human health [15]. The antibacterial activity of four ethanolic extracts of lichens was reported toward Gram-negative and Gram-positive pathogens [16; 17], and lichen active compounds were found to be also effective against ARB (antibiotic-resistant bacteria) strains, such as _Enterococcus faecalis_ and _Staphylococcus aureus_[18; 19; 20; 21]. Among these lichen active compounds, usnic acid is the most studied for its strong biological activities (e.g., antibacterial, antiviral, and antioxidant properties). The antiviral activity of usnic acid is due to the inhibition of transcription, just as the antibacterial activity is given by the inhibition of DNA and RNA synthesis in sensitive bacteria cells. Thus, the antimicrobial activity is expressed mainly by the interference with RNA synthesis and secondarily by the impairment of bacterial DNA replication, especially for Gram-positive bacteria [22]. Considering the growing interest in the antibiotic resistance phenomenon, the reduced sensitivity of pathogens to different antimicrobials, and the lack of new antimicrobial drugs, the research and identification of alternative natural products active alone [23; 24; 25] or in combination with synthetic drugs [26; 27; 28] might be a significant step in the discovery of new antimicrobial compounds. The field of medicine was revolutionized by the discovery of antibiotics, but the increase in their production and their excessive and improper use have caused a constantly increasing selective pressure on bacterial populations, with consequent widespread genes responsible for antibiotic resistance. The massive use of antibiotics is a problem not only in the field of medicine, but also in agriculture, animal husbandry, and aquaculture, and it is increasingly linked to the presence of resistant bacteria in these fields.