Antimicrobial agents from nematode-associated ascomycetes isolated from Heterodera filipjevi

Fungi play an essential role in human civilization and natural ecosystems through their multifaceted roles. Historically, humans have harnessed fungi for food production, medicine, agriculture, and biotechnology. In medicine, fungi have led to the discovery of crucial drugs such as penicillin, cephalosporin, cyclosporine A, and statins, revolutionizing medical treatments and significantly improving public health. However, the rise of antibiotic resistance has become a critical global challenge, threatening the effectiveness of existing drugs and underscoring the urgent need for new molecules to combat antibiotic-resistant organisms.This study focuses on the potential of nematophagous fungi, isolated from the eggs of the cereal cyst nematode Heterodera filipjevi and related species from various regions, to discover compounds with unique antimicrobial properties. The selected methodology included screening in various media, extraction, and isolation of secondary metabolites using classical chromatographic methods. Structure elucidation was performed with a combination of MS, UV, ECD, and 1D and 2D NMR measurements, along with derivatization reactions like Marfey’s or Mosher method in special cases. The isolated metabolites were then biologically characterised against a panel of selected Gram-postive and Gram-negative bacteria, fungi, Caenorhabditis elegans and mammalian cell lines.The results revealed several compounds with significant antimicrobial efficacy, highlighting their potential application within different fields. In particular, the study discusses the feasibility of using these fungi as biocontrol agents against globally relevant agricultural pathogens, particularly plant parasitic nematodes. This represents an environmentally friendly alternative to traditional nematicides, which are prohibited in the majority of countries due to their toxicity on soil microorganisms, vertebrates, and humans.Notably, the genus Polyphilus was found to produce the mycotoxins talaroderxine C and D, which have a dominant effect on Staphylococcus aureus biofilms, along with other intriguing metabolites. Laburnicola nematophila produced the highly antifungal dactylfungins, effective against azole-resistant Aspergillus fumigatus. Preliminary findings for L. nematophila and Polydomus karssenii suggest that many secondary metabolites remain undiscovered and uncharacterised for these taxa, indicating the need for future research.In conclusion, this research highlights the potential of fungi to produce a wide array of natural products with diverse or hidden biological properties. It also emphasizes the need to study fungi comprehensively before developing them into biocontrol agents. The study's findings open new avenues for sustainable agriculture and drug discovery, addressing pressing global challenges such as antibiotic resistance and food security.