SMs can provide self-protection, they may act as mediators for communication with other organisms and are virulence factors for plant and animal pathogens. Moreover, they serve as defense molecules against other microbes (antibiotics) thus contributing to the organization of microbial consortia.
The role of fungal SMs in microbial interactions is mainly referred to the production of antibiotics, recognized as weapons to kill or inhibit competitors. For example, penicillin was discovered for the antibiosis of Penicillium spp. contaminating Staphylococcus spp. Recently their function as signaling molecules in microbial consortia has been demonstrated and several microorganisms have established diverse mechanisms to cope with antimicrobial molecules produced by antagonists. Moreover, some antibiotics also promote the growth of other microbes, act as chemoattractants, or function in a specific communication process (quorum sensing, with the secretion of virulence factors and/or biofilm formation). Another example is that production of 2,4-diacetylphloroglucinol, a specific antibiotic released by Pseudomonas fluorescens, is reduced by fusaric acid formed by Fusarium oxysporum through repression of the responsible biosynthetic genes. In contrast, fusaric acid and other metabolites promote the colonization of F. oxysporum hyphae by P. fluorescens (Fox and Howlett, 2008). Some examples of fungal SMs are given in Fig. 1.
Fig1. Examples of fungal secondary metabolites belonging to the main groups of natural products. Polyketides: (1) Mellein from Aspergillus melleus; (2) Griseofulvin from Penicillium griseofulvum; (3) Patulin from Penicillium spp.; (4)6-pentyl-a-pyrone from Trichoderma spp.; (5)1–hydroxy‐3–methyl anthraquinone from Trichoderma harzianum; (6)Aflatoxin B1 from Aspergillus flavus. Terpenes and terpenoids: (7) T2 Toxin from Fusarium spp.; (8) Gibberellin GA3 from Gibberella fujikuroi; (9) Deoxynivalenol from Fusarium spp. Non-ribosomal peptides: (10) Gliotoxin from Trichoderma and Gliocladium spp.; (11) Alameticin, from Trichoderma viride. Indole alkaloids: (12) Ergotamine from Claviceps purpurea; (13) Fumitremorgin C from Aspergillus fumigatus.
Close physical interactions among fungi and bacteria results in a specific regulation of fungal secondary metabolism that may increase or decrease the production of specific molecules. In some cases, these interactions may also induce the ex-novo production of a single metabolite (i.e., the production of orsellinic acid-derived polyphenols by Aspergillus nidulans) (Kusari et al., 2012).
SMs help fungi to be competitive in an ecological niche. In this context it is important to underline that the effects of natural products are depending on the ecological concentrations and a single metabolite can function as a signal rather than as a toxin. Gradient-dependent effects of phenazine from Pseudomonas aeruginosa on Aspergillus spp. have been demonstrated. A high con centration of this compound is antibiotic while a low to moderate concentration induces sporulation in the fungus. Many examples of induction of fungal SMs when fungi are confronted by other microbes are reported in literature that represent a sort of microbial ‘language’ (Keller, 2019).
Dose-effect responses of fungal metabolites on plant growth and development have also been recognized. This is the case for some Trichoderma- derived SMs (i.e., 6-pentyl-a-pyrone, harzianolide, harzianic acid) that may act as auxin-like compounds. Typically, these molecules have an optimum activity among 10–5 and 10–6 M while are inhibitory at higher concentrations (Vinale et al., 2008; Vinale and Sivasithamparam, 2020).
SMs are further known as virulence factors in plant-fungal interactions and their role in the interaction with animals is also recognized, although not completely elucidated. Moreover, fungal metabolites are involved in the interactions of symbiotic and mycorrhizal or endophytic fungi with plants.
The communication with insects also elicits biosynthesis of SMs in fungi. This interaction is well described in entomopathogenic fungi, especially in Metarhizium spp., Beauveria bassiana and Pochonia spp. Examples of such compounds are destruxins, a cyclic depsipeptide from Metarhizium anisopliae with different modes of actions (i.e., inhibiting V-ATPase, changing ion transport in gut and epithelial tissues, even making behavioral changes), tenellin, beauvericin, and bassianolide from B. bassiana.
References:
Fox, E.M., Howlett, B.J., 2008. Secondary metabolism: Regulation and role in fungal biology. Curr. Opin. Microbiol. 11, 481–487.
Kusari, S., Hertweck, C., Spiteller, M., 2012. Chemical ecology of endophytic fungi: Origins of secondary metabolites. Chem. Biol. 19, 792–798.
Keller, N.P., 2019. Fungal secondary metabolism: Regulation, function and drug discovery. Nat. Rev. Microbiol. 17, 167–180.
Vinale, F., Sivasithamparam, K., Ghisalberti, E.L., et al., 2008. Trichoderma–plant–pathogen interactions. Soil Biol. Biochem. 40, 1–10.
Vinale, F., Sivasithamparam, K., 2020. Beneficial effects of Trichoderma secondary metabolites on crops. Phytother. Res. 34, 2835–2842.
