A metabolite of endophytic fungus Cadophora orchidicola from Kalimeris indica serves as a potential fungicide and TLR 4 agonist

Abstract

Aim To investigate the bioactive metabolite of endophytic fungus from Kalimeris indica. Methods and Results A strain ZJLQ336 was separated from the leaves of K. indica. It was identified as Cadophora orchidicola based on the phylogenetic analysis of ITS‐rDNA sequences. From the fermentation broth a metabolite cercosporamide (compound 1) was isolated, and its structure was determined by spectroscopic analysis. Additionally, this compound was subjected to bioactivity assays, including antifungal activity against seven plant pathogenic fungi, as well as its potential immunoregulatory effects on HEK‐BLUE™‐hTLR4 cells, splenocytes and macrophages. The results showed that cercosporamide had strong growth inhibition against five common plant pathogenic fungi, including Pestalotia diospyri, Botrytis cinerea, Fusarium oxysporum, Sclerotium rolfsii and Penicillum digitatum with EC50 values of 5·29 × 10−3, 0·61, 0·93, 2·89 and 6·7 μg ml−1 respectively. Among which S. rolfsii was one of the main pathogens in K. indica. Moreover, cercosporamide not only significantly stimulated TLR4 activation, splenocyte proliferation and production of cytokines, IFN‐γ and TNF‐α, but also up‐regulated the production of TNF‐α and NO in RAW264.7 macrophages clearly. Conclusions This is the first report of endophytic C. orchidicola from K. indica and its metabolite cercosporamide. The results of pharmacological tests highlight the potential fungicide and TLR4 agonist of cercosporamide. Significance and Impact of the Study This study indicates endophytic fungi are good resources for natural bioactive metabolites. It also suggests that cercosporamide is a potential fungicide and TLR4 agonist.

Antifungal Secondary Metabolites Produced by the Fungal Endophytes: Chemical Diversity and Potential Use in the Development of Biopesticides

“…Moreover, both of them also displayed potent inhibitory effects against mycelial growth of Pythium ultimum, Aphanomyces cochlioides , and R. solani ( Talontsi et al, 2012 ). A metabolite cercosporamide (30) was isolated from the endophytic fungus Cadophora orchidicola from Kalimeris indica ( Wang et al, 2019 ). Antifungal assay revealed that 30 had potent growth inhibition against five plant pathogens, Pestalotia diospyri, B. cinerea, Fusarium oxysporum, Sclerotium rolfsii , and Penicillum digitatum , with EC 50 values of 16.0 × 10 –3 , 1.8, 2.8, 2.89, and 20.2 μM, respectively ( Wang et al, 2019 ).…”

“…A metabolite cercosporamide (30) was isolated from the endophytic fungus Cadophora orchidicola from Kalimeris indica ( Wang et al, 2019 ). Antifungal assay revealed that 30 had potent growth inhibition against five plant pathogens, Pestalotia diospyri, B. cinerea, Fusarium oxysporum, Sclerotium rolfsii , and Penicillum digitatum , with EC 50 values of 16.0 × 10 –3 , 1.8, 2.8, 2.89, and 20.2 μM, respectively ( Wang et al, 2019 ). Two new solanapyrone analogs, solanapyrones N (31) and O (32), and the known solanapyrone C (33), were isolated from Nigrospora sp.…”

Metabolites Produced by Fungi against Fungal Phytopathogens: Review, Implementation and Perspectives

“… Verticillium dahliae A IV 49% [ 109 ] 5-(Undeca-3′,5′,7′-trien-1′-yl) furan-2-carbonate 12% Bicolorin D Saccharicola bicolor Sclerotinia sclerotiorum A IV 13% [ 110 ] IP-A 57% Brefeldin A Cladosporium sp. Aspergillus niger A IV 8-fold [ 111 ] Cercosporamide Cadophora orchidicola Fusarium oxysporum Pestalotia diospyri Botrytis cinerea Sclerotium rolfsii Penicillium digitatum A IV - [ 112 ] Cuminic acid Aspergillus spp. Phytophthora spp.…”

Investigating Host Preference of Root Endophytes of Three European Tree Species, with a Focus on Members of the Phialocephala fortinii—Acephala applanata Species Complex (PAC)

“…Cadophora orchidicola was originally described as a root endophyte of the orchid Platanthera hyperborean [57]. However, the fungus has also been found as an endophyte in the roots of various other plants from various plant families, such as Littorella uniflora (Plantaginaceae), a plant found on the sandy shores of freshwater lakes [58], Kalimeris indica (Asteraceae) [59], Colobanthus quitensis (Caryophyllaceae), and Deschampsia antarctica (Poaceae) in Antarctica [60]. The effects of C. orchidicola on their hosts are not fully understood.…”

“…However, S. involucrata inoculated with the fungus grew to be significantly larger and had a greater biomass. The metabolite cercosporamide, produced by C. orchidicola, was shown to possess fungicidal properties against Pestalotia diospyri, Botrytis cinerea, Fusarium oxysporum, Sclerotium rolfsii, and Penicillium digitatum [59].…”