Antimicrobial and Cytotoxic Activities of the Secondary Metabolites of Endophytic Fungi Isolated from the Medicinal Plant Hyssopus officinalis

Abstract

According to the World Health Organization, it is estimated that by 2050, drug-resistant infections could cause up to 10 million deaths annually. Therefore, finding a new generation of antibiotics is crucial. Natural compounds from endophytic fungi are considered a potential source of new-generation antibiotics. The antimicrobial and cytotoxic effects of ethyl acetate extracts of nine endophytic fungal isolates obtained from Hyssopus officinalis were investigated for bioassay-guided isolation of the natural compounds. An extract of isolate VII showed the highest antimicrobial activities against Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus (30.12 ± 0.20 mm and 35.21 ± 0.20 mm) and Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa (30.41 ± 0.23 mm and 25.12 ± 0.25 mm) among the tested extracts of isolates. Molecular identification of isolate VII confirmed it as Chaetomium elatum based on sequencing of its ITS genes, and it was discovered that this was the first time C. elatum had been isolated from H. officinalis. This isolate was cultured at a large scale for the isolation and identification of the active compound. Penicillic acid was isolated for the first time from C. elatum and its chemical structure was established by NMR spectroscopy. The penicillic acid showed strong antibacterial activities against Bacillus subtilis and Staphylococcus aureus with 20.68 mm and 25.51 mm inhibition zones, respectively. In addition, MIC and MBC values and antibiofilm activities of penicillic acid were determined. It was found that penicillic acid reduced the level of biofilms in proportion to antibacterial activity.

Antimicrobial Action Mechanisms of Natural Compounds Isolated from Endophytic Microorganisms

“…So far, no generalizable chemotypes have emerged among the antibacterial substances isolated from endophytes. It also remains understudied how effectively these compounds penetrate the bacterial cell envelope, which urges more research [ 85 ].…”

“…Penicillic acid (34), isolated from Chaetomium elatum, the endophytic fungi of the medicinal plant Hyssopus officinalis, has demonstrated strong antibacterial activities against Gram-positive (B. subtilis and S. aureus) and Gram-negative (E. coli and P. aeruginosa) bacteria with MIC values of 34-68 µg/mL. Moreover, 34 suppressed both biofilms and planktonic forms [85].…”

“…Indeed, endophytes are a valuable source of metabolites because of their great species diversity and adaptability to a variety of environments [12,13]. Additionally, secondary metabolites of endophytes demonstrate a wide range of biological activities, including antibacterial, antifungal, anticancer, antiviral, antioxidant, anti-inflammatory, immunomodulatory, and hepatoprotective effects [14][15][16]. In recent years, interest in the secondary metabolites of endophytes has significantly increased.…”