深海来源真菌Aspergillus sp .SCSIOW3抗A-beta多肽聚集活性成分的研究

摘要：目的 对一株南海深海来源真菌（Aspergillus sp .SCSIOW3）的抗Aβ聚集活性成分进行了分离、鉴定。方法 利用ThT荧光模型活性追踪分离 Aspergillus sp .SCSIOW3发酵产物中抗Aβ42多肽聚集活性物质,结合理化性质、波谱数据并参阅文献确定活性化合物的结构。结果 从Aspergillus sp .SCSIOW3中分离鉴定了2个具有抗Aβ42多肽聚集活性的桔霉素类衍生物：phenol A acid（1）和Penicitrinone A（2）,其中化合物2在100 uM表现出与阳性对照EGCG同等程度的活性。结论 phenol A acid（1）和Penicitrinone A（2）为橘霉素衍生物,这是首次报导该类化合物的抗Aβ多肽聚集活性,具有潜在的理论和实际应用研究价值。     

Induction of innate immunity by Aspergillus fumigatus cell wall polysaccharides is enhanced by the composite presentation of chitin and beta-glucan

Chitin and β-glucan are conserved throughout evolution in the fungal cell wall and are the most common polysaccharides in fungal species. Together, these two polysaccharides form a structural scaffold that is essential for the survival of the fungus. In the present study, we demonstrated that Aspergillus fumigatus alkali-insoluble cell wall fragments (AIF), composed of chitin linked covalently to β-glucan, induced enhanced immune responses when compared with individual cell wall polysaccharides. Intranasal administration of AIF induced eosinophil and neutrophil recruitment, chitinase activity, TNF-α and TSLP production in mice lungs. Selective destruction of chitin or β-glucan from AIF significantly reduced eosinophil and neutrophil recruitment as well as chitinase activity and cytokine expression by macrophages, indicating the synergistic effect of the cell wall polysaccharides when presented together as a composite PAMP. We also showed that these cell wall polysaccharides induced chitin-specific IgM in mouse serum. Our in vivo and in vitro data indicate that chitin and β-glucan play important roles in activating innate immunity when presented as composite cell wall PAMPs.     

Pituitary aspergillus infection

Fungal infection should be considered in the differential diagnosis of a pituitary or sellar mass, albeit fungal infections involving the pituitary gland and sella are a rare occurrence. We report a case of Aspergillus infection involving the pituitary gland and sellar region discovered in a 74-year-old man. The patient had a history of hypertension, chronic renal disease, autoimmune hemolytic anemia and presented with right eye pain, headaches and worsening hemiparesis. Imaging studies revealed a right internal carotid artery occlusion and an acute right pontine stroke along with smaller infarcts in the right middle cerebral artery distribution. Clinically, the patient was thought to have vasculitis. An infectious etiology was not identified. He developed respiratory distress and died. At autopsy, necrotizing meningitis was discovered. A predominantly chronic inflammatory cell infiltrate consisting of benign-appearing lymphocytes, plasma cells and macrophages was accompanied by acute angle branching, angioinvasive hyphae which were highlighted on Gomori methenamine silver staining and were morphologically consistent with Aspergillus species. In previously reported cases of Aspergillus infection involving the pituitary or sella, most presented with headaches or impaired vision and were not immunocompromised. A transsphenoidal surgical approach is recommended in suspected cases in order to minimize the risk of dissemination of the infection. Some patients have responded well to antifungal medications once diagnosed.     

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Eosinophilic pneumonia was confirmed by bronchoalveolar lavage fluid examination and transbronchial lung biopsy. Aspergillus niger was cultured from the patient's pharyngeal swab and bronchoalveolar lavage fluid. Inhalation bronchoprovocation test with A. niger antigen was positive. Although the patient's condition improved promptly with 10 mg/day prednisolone administration, dry cough recurred approximately 2 months after completion of this therapy. Severe coughing disappeared on oral cleansing with 300 mg/day amphotericin B, and he recovered completely on 100 mg/day amphotericin B administration. Oral cleansing with amphotericin B may be efficacious in preventing relapses of eosinophilic pneumonia caused by allergic reaction to fungal antigen.     

Genetic susceptibility to infections with Aspergillus fumigatus

Infections with the opportunistic mold Aspergillus fumigatus show high morbidity and mortality. Risk factors for the development of invasive aspergillosis are neutropenia, T-cell depletion, CD34-selected stem cell products, corticosteroid therapy, and cytomegalovirus infections.

Recently, a growing number of defined single nucleotide polymorphisms have been described that genetically determine susceptibility to A. fumigatus. This includes genes encoding for cytokines or chemokines and their receptors, toll-like receptor genes, and other genes involved in innate immunity.

This review summarizes the current knowledge about the growing number of genetic markers and their relevance for the course and outcome of infections with A. fumigatus.     

Mycotic Otitis Media in a Harbour Porpoise (Phocoena phocoena)

A 9-year-old by-caught harbour porpoise (Phocoena phocoena) was subject to routine post-mortem examination. Major findings included parasitic infection (Stenurus minor) of the left middle ear and severe mycotic infection of the right middle ear. The morphological appearance of the causative organism was consistent with Aspergillus fumigatus. These pathological findings were likely to have impaired echolocation in this animal and this may have contributed to the by-catch. The ears of marine mammals should be examined routinely during post-mortem investigations.     

Opportunistic Aspergillus pathogens measured in home and hospital tap water by quantitative PCR (QPCR)

Opportunistic fungal pathogens are a concern because of the increasing number of immunocompromised patients. The goal of this research was to test a simple extraction method and rapid quantitative PCR (QPCR) measurement of the occurrence of potential pathogens, Aspergillus fumigatus, A. flavus, A. terreus and A. niger, in home tap water and a hospital water supply.     

Effect of different sample volumes on the DNA extraction of Aspergillus fumigatus from whole blood

Five methods were compared, using conventional PCR, for the isolation of DNA from Aspergillus fumigatus conidia from 1–3-mL samples of whole blood. A lower detection threshold of Aspergillus conidia was achieved using 3-mL rather than 1-mL samples with three of five methods tested.