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Airway remodeling is absent in CCR1-/- mice during chronic fungal allergic airway disease.

Asthmatic-like reactions characterized by elevated IgE, Th2 cytokines, C-C chemokines, eosinophilic inflammation, and persistent airway hyperresponsiveness follow pulmonary exposure to the spores or conidia from Aspergillus fumigatus fungus in sensitized individuals. In addition to these features, subepithelial fibrosis and goblet cell hyperplasia characterizes fungal-induced allergic airway disease in mice. Because lung concentrations of macrophage inflammatory protein-1alpha and RANTES were significantly elevated after A. fumigatus-sensitized mice received an intrapulmonary challenge with A. fumigatus spores or conidia, the present study addressed the role of their receptor, C-C chemokine receptor 1 (CCR1), in this model. A. fumigatus-sensitized CCR1 wild-type (+/+) and CCR1 knockout (-/-) mice exhibited similar increases in serum IgE and polymorphonuclear leukocyte numbers in the bronchoalveolar lavage. Airway hyperresponsiveness was prominent in both groups of mice at 30 days after an intrapulmonary challenge with A. fumigatus spores or conidia. However, whole lung levels of IFN-gamma were significantly higher whereas IL-4, IL-13, and Th2-inducible chemokines such as C10, eotaxin, and macrophage-derived chemokine were significantly lower in whole lung samples from CCR1-/- mice compared with CCR1+/+ mice at 30 days after the conidia challenge. Likewise, significantly fewer goblet cells and less subepithelial fibrosis were observed around large airways in CCR1-/- mice at the same time after the conidia challenge. Thus, these findings demonstrate that CCR1 is a major contributor to the airway remodeling responses that arise from A. fumigatus-induced allergic airway disease.

Animals↗

Protection of PC12 cells from hydrogen peroxide-induced injury by EPS2, an exopolysaccharide from a marine filamentous fungus Keissleriella sp. YS4108.

A number of studies indicate that free radicals are involved in the neurodegeneration in Parkinson's and Alzheimer's diseases. EPS2, an exopolysaccharide with a mean molecular weight of 1.3 x 10(5) Da, was isolated by ion-exchange and sizing chromatography from the culture of Keissleriella sp. YS4108, a marine filamentous fungus. Compositionally, it is composed of galactose, glucose, rhamnose, mannose and glucuronic acid in an approximate proportion of 50:8:1:1:0.4. The protective effects of EPS2 on peroxide hydrogen (H2O2)-induced cell lesion, level of lipid peroxidation, antioxidant enzyme activities were investigated in the rat pheochromocytoma line PC12 cells. Following a 1-h exposure of the cells to H2O2, a significant reduction in cell survival and activities of glutathione peroxidase (GSH-Px) and catalase (CAT), as well as increased levels in malondialdehyde (MDA) production and lactate dehydrogenase (LDH) release were observed. However, preincubation of the cells with EPS2 prior to H2O2 exposure elevated the cell survival and GSH-Px and CAT activities, and decreased the level of MDA and LDH activity in a dose-dependent manner. In conclusion, EPS2 possesses pronounced protective effects against H2O2-induced cell toxicity. The finding is of a higher value in searching for new therapeutic agent for treating oxidative damage-derived neurodegenerative disorders.

Animals↗

Inadvertent administration of intravenous fluids contaminated with fungus.

We present here the case of a patient inadvertently infused with intravenous fluid containing a "fungus ball." Because little is known about such cases, we surveyed 113 infectious diseases specialists for their experiences and ideas on management. Seventy-six responded, of whom 18 had seen a total of 24 cases. Intravenous-fluid containers were often defective, and the fungi involved were usually "contaminants." One patient developed significant fungal infection, and six others had transient symptoms temporally related to the infusion. Most specialists would administer antifungal therapy if symptoms developed, the patient was immunocompromised, or the fungus was pathogenic for humans.

Antifungal Agents↗

Early fumonisin B1 toxicity in relation to disrupted sphingolipid metabolism in male BALB/c mice.

Fumonisin B1 is a mycotoxin produced by Fusarium moniliforme, a common fungus in corn. It is known to cause a variety of diseases, including hepatic and renal degeneration in many species of laboratory and domestic animals. The known biochemical events in fumonisin B1 toxicity involve inhibition of ceramide synthase leading to disruption of sphingolipid metabolism. The effect of fumonisin B1 on ceramide and more complex sphingolipids in mice is not known. Groups of five male BALB/c mice each were injected with fumonisin B1 subcutaneously at doses of 0, 0.25, 0.75, 2.25, and 6.75 mg/kg body weight daily for 5 days. This protocol has been shown to produce a dose-dependent increase in apoptosis in liver and kidney of these animals. In the present study, liver, kidney, and brain were sampled and analyzed for free sphingoid bases and complex sphingolipids one day after the last treatment. A dose-related accumulation of free sphinganine and sphingosine was observed in liver and kidney, but not brain. The maximal increase in free sphinganine in kidney was 10-fold greater than in liver. Total phospholipids increased only in liver, whereas ceramide levels were not consistently altered in liver, kidney, or brain. In liver and kidney, fumonisin B1 treatment increased the sphinganine-containing complex sphingolipids, but no effect was observed on sphingosine-containing complex sphingolipids. No changes in complex sphingolipids were observed in brain. In liver, there was a close correlation between the extent of free sphinganine accumulation, and apoptosis and hepatopathy. This correlation was also evident in kidney but to a lessor extent. Nonetheless, the apoptosis and nephropathy occurred with little or no change in the levels of ceramide or more complex sphingolipids.

Animals↗

A kinase-encoding gene from Colletotrichum trifolii complements a colonial growth mutant of Neurospora crassa.

Colletotrichum trifolii is a fungal pathogen which is responsible for anthracnose disease of alfalfa. To initiate research on molecular communication in this fungus, a kinase-encoding gene (TB3) and the corresponding cDNA were cloned and sequenced. The deduced amino acid sequence of TB3 closely resembles that of a Neurospora crassa serine/threonine protein kinase, COT1, required for hyphal elongation and branching. The C-terminal catalytic domains of TB3 and COT1 are highly conserved but the N-terminal regions are divergent, particularly in the homopolymeric glutamine repeats of TB3. Northern analysis indicated that TB3 expression was highest 1 h after inducing conidial germination and 1 h before germ tubes were first observed. Expression of TB3 transcripts returned to constitutive levels by 4 h after induction of germination. TB3 complemented the cot-I mutant of Neurospora crassa, demonstrating the functional conservation of this kinase between a pathogenic and a saprophytic fungus.

Amino Acid Sequence↗

Genomic evidence for mating abilities in the asexual pathogen Aspergillus fumigatus.

The filamentous fungus Aspergillus fumigatus is one of the causes of invasive lung disease in immunocompromised individuals. It is classified as asexual because no direct observation of mating or meiosis has been reported. Sequencing of the complete genome by an international collaboration, including the Wellcome Trust Sanger Institute (UK) and The Institute for Genomic Research (TIGR, USA), has made most of the genomic sequence information from A. fumigatus publicly available. By searching the incomplete genome sequence of A. fumigatus, I have identified the coding capacity for a set of proteins that could be involved in mating and the pheromone response pathway. These include one putative mating-type gene, one gene encoding a pheromone and two pheromone-receptor genes. The mating-type gene encodes a high-mobility group domain protein exhibiting significant similarity with mating-type proteins from sexually reproducing filamentous ascomycetes. The pheromone gene is predicted to encode a precursor pheromone that is processed by a KEX2-like protease to yield a pheromone that is structurally similar to the alpha-factor of the yeast Saccharomyces cerevisiae. In addition, the deduced gene products of the receptor genes are putative seven-transmembrane proteins, which display a high-level amino acid identity with the a-factor receptor Ste3p and the alpha-receptor Ste2p of S. cerevisiae, respectively. The identification of these homologues suggests the existence of a sexual cycle in A. fumigatus.

Amino Acid Sequence↗

Prosthetic valve endocarditis caused by Trichosporon beigelii.

A case of Trichosporon beigelii prosthetic valve endocarditis is described. Prosthetic valve endocarditis developed in the patient, a 58-year-old woman with a history of rheumatic heart disease, 10 months after mitral valve surgery. A large left atrial fungus ball was present. Cultures of blood and valvular tissue were positive for T. beigelii. The organism was sensitive to amphotericin B, 5-fluorocytosine, ketoconazole, and miconazole.

Endocarditis↗

Invasive hyalohyphomycosis caused by Scopulariopsis brevicaulis in a patient undergoing allogeneic bone marrow transplant.

Scopulariopsis brevicaulis is a common soil saprobic mould. Occasionally, S. brevicaulis has been reported as an etiologic agent of human disease. The spectrum of human mycoses includes toenail infection, hypersensitivity pneumonitis, fungus ball formation in a preformed pulmonary cavity, and, most recently, documented deep tissue infections in immunocompromised hosts. A case of invasive hyalohyphomycosis of the great toe caused by S. brevicaulis is reported in an allogeneic bone-marrow transplant recipient.

Adult↗

Infection of the malaria mosquito Anopheles gambiae with the entomopathogenic fungus Metarhizium anisopliae reduces blood feeding and fecundity.

The entomopathogenic fungus Metarhizium anisopliae is being considered as a biocontrol agent against adult African malaria vectors. In addition to causing significant mortality, this pathogen is known to cause reductions in feeding and fecundity in a range of insects. In the present study we investigated whether infection with M. anisopliae affected blood feeding and fecundity of adult female malaria vectors Anopheles gambiae Giles sensu stricto. Mosquitoes were contaminated with either a low or a moderately high dose of oil-formulated conidia of M. anisopliae, and offered a single human blood meal 48, 72, or 96 h later to assess feeding propensity and individual blood meal size. In a second experiment, individual fungus-infected females were offered a blood meal every third day (to a total of 8 gonotrophic cycles), and allowed to oviposit after each cycle in order to quantify feeding propensity and fecundity. Infected females took smaller blood meals and displayed reduced feeding propensity. It was found that mosquitoes, inoculated with a moderately high dose of fungal conidia, exhibited reduced appetite related to increasing fungal growth. Of the fungus-infected females, the proportion of mosquitoes taking the second blood meal was reduced with 51%. This was further reduced to 35.3% by the 4th blood meal. During 8 feeding opportunities, the average number of blood meals taken by uninfected females was 4.39, against 3.40 (low dose), and 2.07 (high dose) blood meals for the fungus-infected females. Moreover, infected females produced fewer eggs per gonotrophic cycle and had a lower life-time fecundity. Epidemiological models show that both blood feeding and fecundity are among the most important factors affecting the likelihood of a mosquito transmitting malaria, which suggests that this fungus may have potential as biocontrol agent for vector-borne disease control.

Animals↗