The endophytic fungus Cosmosporella sp. VM-42 from Vinca minor is a source of bioactive compounds with potent activity against drug-resistant bacteria

Medicinal plants serve as valuable resources for the isolation of endophytic fungi. <i>Vinca minor</i> is a well-known producer of important vinca alkaloids and emerges as a promising source of endophytic fungi with antibacterial potential and biosynthetic capacity. In this study, we isolated an endophytic fungus from <i>V. minor</i> and identified it as <i>Cosmosporella</i> sp. VM-42<i>.</i> To date, relatively little is known about this fungal genus. The ethyl acetate extract of this isolate selectively inhibited Gram-positive bacteria, such as methicillin-sensitive and methicillin-resistant <i>Staphylococcus aureus</i> (MSSA and MRSA). Therefore, we isolated the most abundant compound from the crude extract and identified it as nectriapyrone with MIC and MBC values ranging from 125 to 62.5 µg/mL against MSSA and MRSA strains. We further sequenced and annotated the 39.07 Mb genome of the isolate, revealing that it encodes 9842 protein-coding genes, including 415 genes for carbohydrate-active enzymes and various biosynthetic gene clusters. Our untargeted metabolomic analysis shows that the fungus produces various secondary metabolites, including cyclodepsipeptides, dimeric naphtho-γ-pyrones, and macrolactones, which are known to have antifungal and antibacterial activities. In addition, we used small-molecule epigenetic modulators to activate the expression of silent biosynthetic gene clusters to broaden the chemical profile of <i>Cosmosporella</i> sp. VM-42<i>.</i> Taken together, we provide a first systematic analysis of <i>Cosmosporella</i> sp. VM-42, and our results show that it is a promising source of compounds with pharmacological potential against drug resistant bacteria.