Introduction
Plants harbor a variety of microorganisms, including epiphytes, endophytes (mostly fungi and bacteria), and pathogenic microorganisms. The term "endophyte" was first introduced by de Bary in 1866, and the association of endophytes with plants dates back 400 million years. Endophytes were initially found in Lolium temulentum in 1904. Historically, endophytes were considered pathogens or parasites due to their extended periods of latency and reduced virulence. Consequently, researchers focus on bioactive metabolites from medicinal plants, especially those capable of surviving unique hostile environmental conditions. These endophytes, that inhabit medicinal plants are a source of producing beneficial compounds, commonly used in developing countries to treat fever, relieve joint pain, and combat seasonal flu novel bioactive agents with therapeutic properties. Microbial endophytes are considered promising novel drug targets because of their structural diversity, low commercial production costs, and broad-spectrum efficacy in treating various medical conditions.
Endophytes as antimicrobial agents
Endophytes maintain a mutualistic association with plants during parts of their life cycle, even when causing internal infections. This interaction leads to the production of numerous secondary metabolites, including quinones, steroids, terpenoids, and xanthones. These novel bioactive agents have promising applications as agrichemicals, antioxidants, cytotoxic agents, antifungals, and other pharmacologically active compounds. Antimicrobial resistance (AMR) is a global concern, particularly due to Mycobacterium tuberculosis's resistance to multiple drugs and the emergence of antibiotic-resistant pathogens like Klebsiella pneumoniae, Salmonella, and Staphylococcus aureus. Consequently, scientists seek novel antimicrobial agents, with endophytes being a promising source due to their ability to survive extreme environmental challenges. Endophytic bacteria, found in all studied plants, contribute significantly to the production of antibacterial agents, with Actinobacteria alone providing about 45% of global antibacterial agents. Fungal endophytes, primarily ascomycetes, produce valuable secondary metabolites such as alkaloids, terpenoids, and phenols, which have shown significant therapeutic potential. Notable antimicrobial compounds from endophytes include ambuic acid (Pestalotiopsis sp.), pestalone (Pestalotiopsis sp.), dicerandrol C (Phomopsis longicolla strain C81), cryptosporioptide (Cryptosporiopsis sp.), pyrrocidine A (Acremonium zeae), etc.
Endophytes as antiviral agents
Conventional chemotherapy has many side effects; therefore, scientists are looking for novel chemotherapeutic agents. Endophytic actinomycetes, particularly Streptomyces aureofaciens, produce diverse secondary metabolites with anticancer activities, that inhibit oncoproteins Bax and bcl-2 in human lung cancer cells. Gram-positive endophytes from Firmicutes phyla are known for plant growth promotion and biocontrol, with Actinobacteria producing antimicrobial and antitumor chemical scaffolds widely used in various industries. Endophyte-derived products have demonstrated greater efficacy and fewer side effects than traditional chemotherapeutic agents, with the first clinically used L-Asparaginase isolated from Escherichia coli. Fungal endophytes, like Aspergillus, Penicillium, and Fusarium spp., produce novel secondary metabolites and enzymes, including chitinase and L-asparaginase, which exhibit significant anti-cytotoxic and myelo-suppressive properties. For instance, Secalonic acid D from Mimusops elengi shows promising cytotoxic activity against HL60 and K562 cells.
Conclusion
The future perspectives of microbial endophytes as antimicrobial and antitumor agents are promising, given their potential to produce novel bioactive compounds. Advancements in genomics and metabolomics could lead to the discovery of new endophytic species as a large number of plants and their associated symbionts still need to be discovered, and their unique secondary metabolites, offer innovative solutions to combat antibiotic resistance and cancer. Additionally, the sustainable and low-cost production of these compounds could revolutionize the pharmaceutical industry, providing more effective and less toxic therapeutic options. Research into the symbiotic relationships and molecular mechanisms of endophytes will further enhance their application in medicine.
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