Layers of Uranium Phosphate Nanorods and Nanoplates Encrusted on Fungus Cladosporium sp. Strain F1 Hyphae.

The hyphae of Cladosporium sp. strain F1 (CFGR 2020-301-00084) were heavily encrusted with pre-synthesized uranium phosphate minerals under a wide range of pH conditions. SEM and TEM images showed that nanorods and nanoplates of uranium phosphate minerals at pH 4 and 5 and at pH 6, 7, and 8, respectively, were tightly adsorbed along the hyphae of Cladosporium sp. strain F1, while only a few uranium phosphate minerals were observed on the hyphae of Aspergillus niger VKMF 1119. Based on the physical mobility and chemical stability of uranium phosphate minerals under in situ oxidizing environmental conditions, the application of Cladosporium sp. strain F1 has potential as a novel strategy for the remediation of uranium contamination in sediments and aquifers under a wide range of pH conditions where larger amounts of phosphate are present in the environment.

Bioactive cyclohexene derivatives from a mangrove-derived fungus Cladosporium sp. JJM22.

Four new cyclohexene derivatives cladoscyclitols A-D (1-4) and one new ribofuranose phenol derivative 4-O-α-D-ribofuranose-2-pentyl-3-phemethylol (5) were obtained from the EtOAC extract of the mangrove-derived endophytic fungus Cladosporium sp. JJM22. The structures were elucidated by extensive NMR and MS analysis, while the absolute configurations of the stereogenic carbons were established based on quantum-chemical electronic circular dichroism calculations or comparison of the optical rotations with those of related compounds. Compounds 2 and 5 displayed potent inhibitory activity against α-glucosidase with the IC50 values of 2.95 and 2.05 µM, respectively.

Antimicrobial activity of endophytic fungi from the medicinal plants Mammea americana (Calophyllaceae) and Moringa oleifera (Moringaceae) / [Actividad antimicrobiana de hongos endófitos de las plantas medicinales Mammea americana (Calophyllaceae) y Moringa oleifera (Moringaceae)].

Introduction: Infectious diseases represent one of the leading causes of death worldwide. Considering the growing global challenge of antimicrobial resistance, research into new sources of potentially effective antimicrobial agents from natural origins is of great importance for world health. Objective: To evaluate the antimicrobial activity of endophytic fungi from Mammea americana and Moringa oleifera upon Staphylococcus aureus (ATCC 29213), S. aureus (resistant strain USb003), Escherichia coli (ATCC 25922), and E. coli (resistant strain USb007). Materials and methods: We isolated endophytic fungi from the leaves, seeds, and stems of the two plants under study. We evaluated their antimicrobial activity through the formation of sensitivity haloes in dual tests in vitro, as well as in trials using crude ethanolic extracts from the endophytes. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and cytotoxicity o the substances were analyzed. Results: Three ethanolic extracts of Penicillium sp., Cladosporium (001), and Cladosporium (002) exhibited the greatest inhibition halos in sensitive and resistant strains of E. coli and S. aureus. The MIC and CBM found were statistically significant (p≤0.05) compared with the gentamicin control. Furthermore, the cytotoxicity test results of CC50>1,000 demonstrated that the endophytic fungi studied exhibit bactericidal characteristics without causing unintended damage. Conclusion: The endophytic fungi M. oleifera and M. americana represent a source of active secondary metabolites with antimicrobial and non-toxic properties. In light of these findings, further research should proceed with chemical identification of the compounds and the study of their mechanisms of action, especially given the paucity of current scientific knowledge concerning the isolation of endophytes in these plants.

Introducción. Las enfermedades infecciosas son una causa importante de muertes en el mundo. La resistencia antimicrobiana es un problema global, por lo que es conveniente la investigación de nuevas fuentes de agentes antimicrobianos de origen natural potencialmente efectivos. Objetivo. Evaluar la actividad antimicrobiana de hongos endófitos de Mammea americana y Moringa oleifera en la cepa sensible (ATCC 29213) y en la cepa resistente (USb003) de Staphylococcus aureus, así como en la cepa sensible (ATCC 25922) y la cepa resistente (USb007) de Escherichia coli. Materiales y métodos. Se aislaron 14 hongos endófitos de las hojas, semillas y tallos de las dos plantas en estudio. Se evaluó su actividad antimicrobiana mediante la formación de halos de sensibilidad por ensayo dual in vitro y pruebas con extractos etanólicos crudos provenientes de los endófitos a los que se les evaluó la concentración mínima inhibitoria (CMI), la concentración bactericida mínima (CBM) y la citotoxicidad. Resultados. Tres extractos etanólicos de Penicillium sp., Cladosporium sp. (001) y Cladosporium sp. (002) presentaron mayores halos de inhibición en cepas sensibles y resistentes de E. coli y S. aureus. La CMI y la CBM halladas fueron estadísticamente significativas (p≤0,05), comparadas con el control de gentamicina. Las pruebas de citotoxicidad (concentración citotóxica, CC50>1.000) demostraron que los hongos endófitos poseen características bactericidas y no ocasionan daño alguno. Conclusión. Se halló una fuente de metabolitos secundarios activos con propiedades antimicrobianas y no tóxicas en los hongos endófitos de M. oleifera y M. americana; estos hallazgos son importantes para continuar con la identificación química de los compuestos y el estudio de sus mecanismos de acción en estas plantas en las que el aislamiento de endófitos ha sido escaso.

Thiocladospolide E and cladospamide A, novel 12-membered macrolide and macrolide lactam from mangrove endophytic fungus Cladosporium sp. SCNU-F0001.

Chemical investigation of the mangrove endophytic fungus Cladosporium sp. SCNU-F0001 resulted in the isolation and identification of a new macrolide compound named thiocladospolide E (1) and a novel macrolide lactam named cladospamide A (2), along with the known cladospolide B (3). The structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and HPLC analysis after chemical derivatization. All compounds were tested for their antibacterial and cytotoxic activity.

Cladosporamide A, a new protein tyrosine phosphatase 1B inhibitor, produced by an Indonesian marine sponge-derived Cladosporium sp.

Cladosporamide A (1), a new protein tyrosine phosphatase (PTP) 1B inhibitor, was isolated together with a known prenylated flavanone derivative (2) from the culture broth of an Indonesian marine sponge-derived Cladosporium sp. TPU1507 by solvent extraction, ODS column chromatography, and preparative HPLC (ODS). The structure of 1 was elucidated based on 1D and 2D NMR data. Compound 1 modestly inhibited PTP1B and T-cell PTP (TCPTP) activities with IC50 values of 48 and 54 µM, respectively. The inhibitory activity of 2 against PTP1B (IC50 = 11 µM) was approximately 2-fold stronger than that against TCPTP (IC50 = 27 µM).

A new antiviral pregnane from a gorgonian-derived Cladosporium sp. fungus.

A new pregnane, 3α-hydroxy-7-ene-6,20-dione (1), and five known steroids (2-6), along with one known steroidal glycoside (7) were obtained from the fungus Cladosporium sp. WZ-2008-0042 cultured from a gorgonian Dichotella gemmacea collected from the South China Sea. The structure and absolute configuration of the new compound (1) were elucidated by comprehensive spectroscopic data and X-ray diffraction data. The compound has a rare configuration of 3α-OH that is different from most of pregnanes. All of the isolated compounds were evaluated for their antiviral activities against respiratory syncytial virus (RSV). Among them, 1 exhibited potential antiviral activity with the IC50 value of 0.12 mM.

Antioxidant and in vivo genoprotective effects of phenolic compounds identified from an endophytic Cladosporium velox and their relationship with its host plant Tinospora cordifolia.

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia (Willd. Hook. f. & Thomson; family: Menispermaceae), has a long history of use in various traditional medicinal systems including "Ayurveda". It is reported to possess anticancer, antidiabetic, antimicrobial, antispasmodic, and antiinflammatory activities. T. cordifolia has also been well documented for production of various bioactive metabolites and their antioxidant activity, but the microorganisms associated with it have been least explored for the same properties. AIM OF THE STUDY: Aim of the present study was to evaluate antioxidant and in vivo genoprotective potential of phenolic compounds produced by an endophytic fungus Cladosporium velox TN-9S isolated from T. cordifolia. MATERIALS AND METHODS: The isolate of C. velox TN-9S was cultivated in malt extract medium and extracted with ethyl acetate. Total phenol content was determined by Folin Ciocalteu reagent. The antioxidant activity was measured in terms of DPPH and FRAP assay. The in vivo genoprotective activity was assessed using fish Channa punctatus as model. Identification of phenolic compounds was carried out using RP-HPLC. The fungal extract was evaluated for biosafety using Salmonella typhimurium His- strain and CHO cell lines for mutagenicity and cytotoxicity, respectively. RESULTS: The total phenolic content in the ethyl acetate extract of the fungus was determined to be 730µg gallic acid equivalent/mL. The extract evinced significant antioxidant activity with IC50 value of 22.5µg/mL in DPPH scavenging assay. The phenolic extract showed good in vivo genoprotective activity against the genetic damage induced in fish C. punctatus after treatment with a non-ionic surfactant 4-nonylphenol. RP-HPLC analysis revealed the presence of peaks corresponding to various phenolic compounds in the extract. Mutagenicity and cytotoxicity results revealed the extract to be nonmutagenic and non cytotoxic in nature. CONCLUSION: The results indicate the potential of an endophytic C. velox isolated from T. cordifolia as a producer of phenolic compounds with antioxidant and genoprotective activities which could be exploited in pharmaceutical industry. The ability of endophytes to produce similar compounds as the host, is also revealed in the present study.

Endophytic fungi associated with Sudanese medicinal plants show cytotoxic and antibiotic potential.

In this study, we isolated 15 endophytic fungi from five Sudanese medicinal plants. Each fungal endophytic strain was identified by sequencing of internal transcribed spacer (ITS) regions of rDNA. Ethyl acetate extracts were prepared from each endophyte cultivated in vitro and tested for their respective antibacterial activities and antiproliferative activities against human cancer cells. Antibacterial screening was carried out against two bacterial strains: Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus, by the broth dilution method. Cell viability was evaluated by the MTT procedure after exposure of MCF7 breast cancer cells and HT29 or HCT116 human colon adenocarcinoma cells to each endophytic extract. Of interest, Byssochlamys spectabilis isolated from Euphorbia prostata showed cytotoxicity (IC50 = 1.51 ± 0.2 µg mL(-1)) against MCF7 cells, but had a low effect against HT29 or HCT116 cells (IC50 > 20 µg mL(-1)). Cladosporium cladosporioides 2, isolated from Vernonia amygdalina leaves, showed antiproliferative activities against MCF7 cells (IC50 = 10.5 ± 1.5 µg mL(-1)) only. On the other hand, B. spectabilis and Alternaria sp. extract had antibacterial activities against the S. aureus strain. The findings of this work revealed that endophytic fungi associated with medicinal plants from Sudan could be considered as an attractive source of new therapeutic compounds.

Chemical and Biological Study of Cladosporin, an Antimicrobial Inhibitor: A Review.

. Natural antifungal agents are generally broad-spectrum compounds with low mammalian and environmental toxicity. Cladosporin is a naturally occurring fungal metabolite mainly isolated from the endophytic fungus Cladosporium cladosporioides. This review article summarizes the chemistry and biological - properties of cladosporin covering references published from 1971-2016, including the source, phytochemical characterization, biosynthesis, total synthesis, structure and activity (SAR), and biological activity of cladosporin. Cladosporin exhibited potent antibacterial, antifungal, insecticidal, and anti-inflammatory activities, as well as plant growth regulatory effects. More importantly, cladosporin was identified as having potent, nanomolar, antiparasitic activity against both Plasmodiumfalciparum blood and liver stages via specific inhibition of protein synthesis. This provides a new approach for the design of isocoumarin- based compounds for the treatment of malaria. Herbicidal activity and antifungal activity against Cryptococcus neoformans (C50 value of 17.7 µg/mL) of cladosporin are also described here in the review for the first time. Cladosporin selectively inhibited the growth of a monocot (agostis) and showed no activity against a dicot (lettuce), which indicates its great potential as a selective herbicide for monocots in agriculture use. The above data suggest that cladosporin has great potential utility as a lead compound in the development of agrochemicals against certain plant pathogens and pharmaceuticals against drug-resistant bacteria and parasites.

Identification of the hydroxamate siderophore ferricrocin in Cladosporium cladosporioides.

The hydroxamate siderophore ferricrocin was identified in Cladosporium cladosporioides growth medium by solid phase extraction and ultra high pressure liquid chromatography coupled to a time of flight mass spectrometer (UHPLC/QTOF-MS). Both desferricrocin and ferricrocin were detected in the extracellular medium assisted by high resolution mass spectrometry. This is the first identification of a hydroxamate siderophore in Cladosporium cladosporioides. This finding emphasizes the common meaning of ferricrocin in fungi.

Secondary mould metabolites of Cladosporium tenuissimum, a hyperparasite of rust fungi.

Investigation of the extracts of a culture of Cladosporium tenuissimum, a known hyperparasite of several rust fungi, gave rise to the isolation of cladosporols B-E (2-5). Their structure and stereochemistry were elucidated on the basis of 1H and 13C NMR evidence and CD measures. Cladosporols 1-5 were active in inhibiting the urediniospore germination of the bean rust agent Uromyces appendiculatus.

Differential regulation of CD3- and CD28-induced IL-2 and IFN-gamma production by a novel tyrosine kinase inhibitor XR774 from Cladosporium cf. cladosporioides.

Inhibition of CD28 signalling after an immune response impedes T cell activation and can lead to immunosuppression. To identify inhibitors of anti-CD28 induced IL-2 production, a library of fungal metabolites was screened in a cell-based, high throughput assay. A reduced novel benzofluoranthene, tentatively named as (6bS, 7R, 8S)-7-methoxy-4, 8, 9-trihydroxy-1, 6b, 7, 8-tetrahydro-2H-benzo[j] fluoranthen-3-one (XR774), from Cladosporium cf. cladosporioides, was isolated. XR774 inhibited IL-2 mRNA and protein expression induced by anti-CD28 and anti-CD3 but had no effect on IL-2 induction by PMA and ionomycin. Moreover, XR774 inhibited the activity of the tyrosine kinases, Fyn, Lck, Abl and epidermal growth factor receptor (EGFR) with nanomolar activity, whereas micromolar concentrations of XR774 were ineffective on the serine-threonine kinase, PKA. Kinetic analysis of Fyn kinase inhibition was consistent with XR774 as a competitive inhibitor with respect to ATP. In peripheral blood, mononuclear cells (PBMC), XR774 inhibited anti-CD3 and anti-CD28 induced IL-2 and IL-2R alpha chain (CD25) expression but was consistently less active for inhibition of IFN-gamma production. On stimulation with PMA and anti-CD28, XR774 inhibited IL-2 production but had no effect on CD25 expression and enhanced IFN-gamma production. In contrast, the ansamycin, geldanamycin, inhibited both IL-2 and IFN-gamma production induced by anti-CD3 and anti-CD28 or PMA and anti-CD28. No significant associated cytotoxicity or inhibition of protein synthesis was observed at concentrations up to 14 microM. Thus, XR774 represents a novel class of pharmacological agent with selective biological activities that distinguish it from other natural product inhibitors, such as the ansamycins.