Mucoricin is a ricin-like toxin that is critical for the pathogenesis of mucormycosis.

Fungi of the order Mucorales cause mucormycosis, a lethal infection with an incompletely understood pathogenesis. We demonstrate that Mucorales fungi produce a toxin, which plays a central role in virulence. Polyclonal antibodies against this toxin inhibit its ability to damage human cells in vitro and prevent hypovolemic shock, organ necrosis and death in mice with mucormycosis. Inhibition of the toxin in Rhizopus delemar through RNA interference compromises the ability of the fungus to damage host cells and attenuates virulence in mice. This 17 kDa toxin has structural and functional features of the plant toxin ricin, including the ability to inhibit protein synthesis through its N-glycosylase activity, the existence of a motif that mediates vascular leak and a lectin sequence. Antibodies against the toxin inhibit R. delemar- or toxin-mediated vascular permeability in vitro and cross react with ricin. A monoclonal anti-ricin B chain antibody binds to the toxin and also inhibits its ability to cause vascular permeability. Therefore, we propose the name 'mucoricin' for this toxin. Not only is mucoricin important in the pathogenesis of mucormycosis but our data suggest that a ricin-like toxin is produced by organisms beyond the plant and bacterial kingdoms. Importantly, mucoricin should be a promising therapeutic target.

Augmented anticancer activity of curcumin loaded fungal chitosan nanoparticles.

Fungal chitosan (FCt) from Amylomyces rouxii, with 88.7% deacetylation degree and 112.4 kDa molecular weight, was utilized for nanoparticles (NPs) formation via ionic gelation. FCt-NPs were employed as carriers for curcumin (CUR) to augment its availability and anticancer bioactivity. The synthesis of CUR/FCt-NPs composite was succeeded as evidenced from their FTIR spectra. The scanning micrographs of synthesized CUR/FCt-NPs indicated their spherical shapes and well-distribution; they had average diameters of 115 ± 21 nm and positive zeta potentials of +33.8 mV. The NPs loading capacity for CUR was 21.6% and the encapsulation efficiency reached 83.8%. The CUR was vastly released in the beginning 5 h then gradually released up to 90 h, with higher release in pH 5.2 than in pH 7.0. The treatment of cancer cells, HCT-116 and A-549, with CUR/FCt NPs lead to time-dependent decrement of cells' viability; the dead cells were 67.6% from HCT-116 and 73.8% from A-546 after 96 h of exposure. Fluorescent imaging indicated that most cancer cells entered the apoptosis phase after treatment with 150 µM of CUR/FCt-NPs for 72 h. The efficiency of FCt-NPs was proved as carriers for loading CUR and augmenting its anticancer activity toward human cancer cells, using these natural and biosafe agents.

Adsorption of cadmium from aqueous solutions by novel Fe3O4- newly isolated Actinomucor sp. bio-nanoadsorbent: functional group study.

A novel bio-nanocomposite was prepared by the combination of fungal biomass and Fe3O4 magnetic nanoparticles. The result of XRD and EDAX analysis indicated that Fe3O4 Actinomucor sp. bio-nanoadsorbent was prepared. Our experiments showed that the adsorption kinetics and isotherm of this material comply with the pseudo-second-order and the Langmuir models, respectively. The maximum adsorption capacity (qmax) of this novel bio-nanoadsorbent was obtained as 29.49 mg/g. The thermodynamic analysis revealed that the adsorption of Cd2+ is spontaneous and exothermic. The optimum temperature, initial concentration, contact time and pH for adsorption system of cadmium were about 45 °C, 400 mg/L, 120 min and 7, respectively. Pretreatment of adsorbent by NaOH and SDS significantly increased cadmium adsorption capacity. SEM images showed that Fe3O4 nanoparticles were immobilized successfully on the fungus cell surface. Contribution of the carboxyl, hydroxyl, amine and Fe-O functional groups of the bio-nanoadsorbent in the binding to cadmium ions was revealed by FTIR analysis. Results from regeneration studies indicated reusability of the adsorbent up to 91%. According to experimental results, it could be claimed that bio-nanocomposite of Fe3O4-Actinomucor sp. is a novel efficient adsorbent for removal of metal ions from aqueous solutions, and hence it has potential to be used in the environmental pollution cleanup programs.

Mucormicosis rino-órbito-cerebral de origen dental / Rhino-orbito-cerebral mucormycosis from dental origin: Case report

Resumen La mucormicosis es una infección aguda causada por hongos oportunistas pertenecientes al orden de los mucorales, que afecta principalmente a pacientes diabéticos e inmunosuprimidos. Se reporta el caso de un hombre diabético de 63 años de edad, que se extrajo una pieza dental por sus propios medios y, posteriormente, desarrolló una mucormicosis rino-órbito-cerebral con afección cutánea y palatina. La especie aislada mediante cultivos micológicos fue Rhizopus sp.

Abstract Rhino-orbito-cerebral mucormycosis from dental origin is an acute infection caused by opportunistic fungi belonging to the order of Mucorales, which affects mainly diabetic and immunocompromised patients. We report the case of a 63-year old diabetic man who performed a dental extraction on himself by his own means and subsequently developed a rhino-orbito-cerebral mucormycosis with cutaneous and palatal affection. The species isolated in the mycological culture was Rhizopus sp.

Natural Origin Lycopene and Its "Green" Downstream Processing.

Lycopene is an abundant natural carotenoid pigment with several biological functions (well-known for its antioxidant properties) which is under intensive investigation in recent years. Lycopene chemistry, its natural distribution, bioavailability, biological significance, and toxicological effects are briefly outlined in the first part of this review. The second, major part, deals with various modern downstream processing techniques, which are assessed in order to identify promising approaches for the recovery of lycopene and of similar lipophilic compounds. Natural lycopene is synthesized in plants and by microorganisms, with main representatives of these two categories (for industrial production) tomato and its by-products and the fungus Blakeslea trispora, respectively. Currently, there is a great deal of effort to develop efficient downstream processing for large scale production of natural-origin lycopene, with trends strongly indicating the necessity for "green" and mild extraction conditions. In this review, emphasis is placed on final product safety and ecofriendly processing, which are expected to totally dominate in the field of natural-origin lycopene extraction and purification.

Bioactive depsidones from the fungus Pilobolus heterosporus.

A new aromatic ester, pilobolusate (1), four new depsidones, pilobolusones A-D (2-5), five known depsidones, (6-10), and ergosterol were isolated from the fungus Pilobolus heterosporus. Their structures were established on the basis of spectroscopic data. Compounds 2 and 4-9 showed cytotoxicity against three cancer cell lines (KB, MCF-7, and NCI-H187) with IC50 values in the range of 9.94-97.42 µM. In addition, compounds 2, 5, 9, and 10 exhibited antimalarial activity against Plasmodium falciparum with IC50 values ranging from 3.67-23.56 µM.

Cytotoxic lasiodiplodin derivatives from the fungus Syncephalastrum racemosum.

Chemical investigation of fungal biomass of the fungus Syncephalastrum racemosum led to the isolation of new natural products (3R),(5S)-5-hydroxy-de-O-methyllasiodiplodin (1), 6-oxode-O-methyllasiodiplodin (2), in addition to five known compounds, de-O-methyllasiodiplodin (3), lasiodiplodin (4), (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin (5), ergosterol (6), and ergosterol peroxide (7). Their structures were elucidated by spectroscopic techniques. The absolute configuration of 1 was determined by a modified Mosher's method. Compound 1 showed cytotoxicity against cholangiocarcinoma, KKU-M139, KKU-M156, and KKU-M213 cell lines with IC(50) values in the range of 14-19 µg/mL, while 3 showed cytotoxicity against KB, BC1, and NCI-H187 cell lines with IC(50) values of 12.67, 9.65, and 11.07 µg/mL, respectively.

Antimutagenic activity of lipidovit.

Antimutagenic properties of Lipidovit produced from the biomass of Blakeslea trispora fungi was studied by its effect on induction of chromosome aberrations by chemical mutagens dioxidine and cyclophosphamide in mouse bone marrow cells. Antimutagenic activity of Lipidovit depended on the scheme of treatment. It was maximum during pretreatment of animals (5 day) or administration in combination with mutagens (5 days). The preparation was ineffective after single administration in combination with mutagens. Lipidovit exhibited no comutagenic properties.

Purification and kinetics of a raw starch-hydrolyzing, thermostable, and neutral glucoamylase of the thermophilic mold Thermomucor indicae-seudaticae.

The purified glucoamylase of the thermophilic mold Thermomucor indicae-seudaticaehad a molecular mass of 42 kDa with a pI of 8.2. It is a glycoprotein with 9-10.5% carbohydrate content, which acted optimally at 60 degrees C and pH 7.0, with a t(1/2) of 12 h at 60 degrees C and 7 h at 80 degrees C. Its experimental activation energy was 43 KJ mol(-1) with temperature quotient (Q(10)) of 1.35, while the values predicted by response surface methodology (RSM) were 43 KJ mol(-1) and 1.28, respectively. The enzyme hydrolyzed soluble starch at 50 degrees C (K(m) 0.50 mg mL(-1) and V(max) 109 micromol mg(-1) protein min(-1)) and at 60 degrees C (K(m) 0.40 and V(max) 143 micromol mg(-1) protein min(-1)). The experimental K(m) and V(max) values are in agreement with the predicted values at 50 degrees C (K(m) 0.45 mg mL(-1) and V(max) 111.11 micromol mg(-1) protein min(-1)) and at 60 degrees C (K(m) 0.36 mg mL(-1)and V(max) 142.85 micromol mg(-1) protein min(-1)). An Arrhenius plot indicated thermal activation up to 60 degrees C, and thereafter, inactivation. The enzyme was strongly stimulated by Co(2+), Fe(2+), Ag(2+), and Ca(2+), slightly stimulated by Cu(2+) and Mg(2+), and inhibited by Hg(2+), Zn(2+), Ni(2+), and Mn(2+). Among additives, dextran and trehalose slightly enhanced the activity. Glucoamylase activity was inhibited by EDTA, beta-mercaptoethanol, dithiothreitol, and n-bromosuccinimide, and n-ethylmaleimide inhibited its activity completely. This suggested the involvement of tryptophan and cysteine in catalytic activity and the critical role of disulfide linkages in maintaining the conformation of the enzyme. The enzyme hydrolyzed around 82% of soluble starch and 65% of raw starch (K(m) 2.4 mg mL(-1), V(max) 50 micromol mg(-1) protein min(-1)), and it was remarkably insensitive to glucose, suggesting its applicability in starch saccharification.

Preliminary safety assessment of an arachidonic acid-enriched oil derived from Mortierella alpina: summary of toxicological data.

An arachidonic acid-enriched oil (AA-oil), derived from Mortierella alpina was subjected to a programme of studies to establish its preliminary safety for use in infant nutrition. This was addressed at two levels: (1) HPLC analysis of metabolites produced by the production strains at various conditions, and (2) an evaluation of the toxicity of the final product. The following studies were carried out on the AA-oil: gene mutation assays in bacteria and mammalian cells in vitro; chromosome aberration assays both in vitro and in vivo and acute and subacute (4-wk) oral toxicity in the rat. No known mycotoxins were produced by the production strains under the conditions tested. Further, the oil did not show mutagenic or clastogenic activity and the acute oral toxicity, expressed as the LD50 value, exceeded 20 ml/kg body weight, that is, 18.2 g/kg body weight. In the subacute oral toxicity study the AA-oil was tested as such and in combination with a docosahexaenoic-enriched oil (DHA-oil) derived from fish oil at a ratio of 2:1 (AA:DHA). This was done because high dose levels of AA may result in adverse effects; DHA can compensate for these effects. Furthermore, human milk contains both AA and DHA at a ratio of AA:DHA of 2 to 3:1. No obvious signs of toxicity were observed. Levels of phospholipids and triglycerides tended to be decreased in the highest dose groups. The no-observed-adverse-effect level of the AA-oil in the subacute 4-wk toxicity study was placed at the highest levels tested, namely 3000 mg AA-oil/kg body weight/day as such and in the combination of 3000 mg AA-oil and 1500 mg DHA-oil/kg body weight/day. This corresponds to an intake of 1000 mg AA/kg body weight/day, which represents approximately 37 times the infant intake of AA in human milk.