Abstract
The prevalence of multidrug-resistant Mycobacterium tuberculosis, the bacterium that causes tuberculosis, poses a significant public health challenge. While current drug combinations have been effective in controlling tuberculosis, the emergence of resistance greatly limits treatment options and highlights the need for new therapeutic approaches. Recent advances in metabolomics indicate that microorganisms, particularly fungi, harbour a vast and largely unexplored reservoir of unique chemical structures that could serve as potential drug candidates. However, no fungal secondary metabolite-derived drugs targeting mycobacterial infections have made it to clinical trials. This study aimed to employ a metabolomics strategy to profile secondary metabolites with anti-mycobacterial activity from marine endophytic fungi. We identified a marine-derived endophytic fungal isolate Engyodontium album using the internal transcribed spacer (ITS) ITS sequence region. The crude extracts of the marine fungal endophyte were evaluated for antimicrobial activity against Mycobacterium smegmatis MC2155; and displayed a minimum inhibitory concentration (MIC) of 31.25 μg/mL. Additionally, 16 putative secondary metabolites annotated from a feature-based molecular network of the bioactive fraction were identified using High-resolution Liquid Chromatography-Mass Spectrometry. The diverse profile of bioactive compounds included those previously reported to exhibit anti-mycobacterial activities, such as weak acids (e.g., linoleic acid) and phenylalanine derivatives (including N-acetyl-1-phenylalanine, N-(1-deoxy-1-fructosyl) phenylalanine, and phenylalanine–prolyl). Based on the observed activity against M. smegmatis and the presence of these various bioactive compounds, it can be concluded that this isolate has the potential to serve as a source of chemical scaffolds for the development of new and effective anti-tuberculosis drug candidates.
Keywords: Mycobacterium tuberculosis, marine endophytic fungi, secondary metabolite, untargeted metabolomics.