一株海兔来源真菌 Aspergillus terreus丁内酯类化合物及其生物活性研究

摘要：目的 在生物活性和化学方法指导下,从1株海兔来源真菌 Aspergillus terreus (RA29-5)中分离鉴定海洋天然产物,并对其进行生物活性评价。方法 运用硅胶柱层析、Sephadex LH-20凝胶柱层析和HPLC等方法分离纯化化合物,利用NMR等现代波谱分析方法,对化合物进行结构鉴定,并对化合物进行抗菌、卤虫致死和斑马鱼胚胎毒性活性评价。结果 鉴定了 9 个丁内酯类化合物 (1～9) 的结构;抗菌活性表明,除化合物 6 和 9 外,所有化合物对四株致病细菌白色葡萄球菌 Staphylococcus epidermidis、金黄色葡萄球菌 Staphylococcus aureus、蜡状芽孢杆菌 Bacillus subtilis 和四联球菌 Tetragenococcus halophilus 都显示一定的抗菌活性;化合物 1～4 和7均对真菌芒果叶枯菌 Pestalotia mangiferae 显示抗菌活性;特别的,化合物 7 对测试的13株致病菌都具有广谱地抗菌活性,其MIC值在1.11~8.88 μmol/L之间;此外,还对化合物的抗菌活性构效关系进行了初步探讨。结论 海兔来源真菌 A. terreus (RA29-5) 可产生结构多样的丁内酯类化合物,该类化合物具有开发成抗菌剂的潜力。     

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。     

Small-Bowel Infarction From Disseminated Aspergillosis

INTRODUCTION: Despite the use of new, effective drugs, the disseminated invasive aspergillosis often remains lethal in neutropenic patients. Diagnosis is difficult because early symptoms are nonspecific. New tools could help in diagnosis and lead to early surgery when needed.METHODS: A neutropenic patient developed an acute abdomen. CT findings were a diffuse, small-bowel distention with a thickened, distal, ileum wall. Emergency surgery was performed with resection and immediate anastomosis of the distal ileum. Pathology of the small bowel showed a wall necrosis and invasion by Aspergillus fumigatus.RESULTS: The postoperative course was uneventful except for persisting diarrhea secondary to a coexistent infection with Clostridium difficile. Aspergillus antigene in serum was positive, whereas neither pulmonary nor central nervous system aspergillosis was observed on CT scan.CONCLUSIONS: This diagnosis should be considered when neutropenic patients show abdominal pain and distention with fever. Repetition of Aspergillus antigenemia, search for others aspergillosis localizations, CT scan, and colonoscopy with biopsies should be performed until diagnosis allows the administration of early antifungal therapy.     

Precipitins to an aflatoxin-producing strain of aspergillus flavus in patients with malignancy

Summary Serum samples from 121 patients in whom malignant disease had been diagnosed, were assayed for precipitins to fungal isolates from leukemia-associated environments. Control sera were from age-, sex-, and race-matched patients with no history of malignant disease. Sera from 36 (30%) malignancy patients and seven (6%) controls yielded a precipitin band to an aflatoxin-producing Aspergillus flavus isolate from a leukemia-associated house ², p<0.05%). No significant numbers of precipitins were obtained to either of the other fungal isolates from that and another such house.Although A. fumigatus has frequently been incriminated as a source of infection in patients with malignancy, only 9% of malignancy patients had a precipitin response to it, as did 1.6% of controls. Also, the presence of the precipitins to A. flavus was not connected with past radiation or imunosuppressive therapy. However, among patients with precipitins to A. fumigatus there was a higher death rate in the year following the study. Precipitins to A. flavus may be related to heavy environmental exposure possibly leading to aflatoxin exposure which may contribute to development of malignancy through immunosuppressive effects.     

The Genomic Regions That Contain Ochratoxin A Biosynthetic Genes Widely Differ in Aspergillus Section Circumdati Species

Aspergillus section Circumdati includes 27 species, some of which are considered ochratoxin A (OTA) producers. However, there is considerable controversy about their potential OTA synthesis ability. In this work, the complete genomes of 13 species of Aspergillus section Circumdati were analyzed in order to study the cluster of OTA biosynthetic genes and the region was compared to those previously reported in A. steynii and A. westerdijkiae. The results obtained reveal that the genomes of some species in this section, including A. affinis, A. cretensis, A. elegans, A. muricatus, A. pulvericola, A. roseoglobulosus, and A. subramanianii, contain a potentially functional OTA biosynthetic cluster. Therefore, they might be able to synthesize the toxin. On the contrary, A. melleus, A. ochraceus, A. ostianus, A. persii, A. sclerotiorum, A. sesamicola, and A. westlandensis contain a truncated version of the cluster that lacks many of the genes involved in OTA biosynthesis, which might be related to their inability to produce OTA. The gain/loss pattern is different in all species, which suggests that the genetic evolution of this region might be due to independent events.     

实时定量PCR检测人全血标本中烟曲霉基因组载量的方法及临床应用

目的建立实时定量PCR（RQ-PCR）快速检测人全血标本中烟曲霉基因组载量的方法及进行初步临床应用。方法基于烟曲霉多拷贝基因ITSl-5．8S基因设计引物和TaqMan探针,用QIAamp^DNA Blood Mini Kit提取烟曲霉基因组DNA,建立20μlRQ-PCR反应体系,对含有不同载量烟曲霉基因组的模拟人全血标本和66份外科发热患者全血标本进行烟曲霉基因组的定量检测。结果检测限为10^-1基因组／μl上机待测液（即约78CFU／ml全血）;检测特异度和灵敏度分别为94．25％和99．04％,阳性预告值和阴性预告值分别为97．63％和97．62％;测定结果的平均相对误差为（3．67±13．19）％;批内及批间平均重复性变异系数分别为（12．38±1．53）％和（16．27±2．72）％;人血标本中烟曲霉基因组平均回收率为（107．81±25．92）％,回收率平均变异系数为（26．24±5．62）％。66份外科发热患者血标本中未检测出烟曲霉基因组。结论RQ-PCR可以快速、特异、灵敏地定量检测人血标本中烟曲霉基因组的载量,且有着较好的准确度与精密度。本研究外科发热患者血中未检测到烟曲霉基因组。     

烟曲霉致病相关因子的研究进展

毒力因子是在病原体适应生存环境的过程中产生.烟曲霉毒力是多因素相关的,包括微小的孢子结构使之能够吸入到达宿主的肺泡,耐热特征,疏水性,快速的繁殖速度以及抵抗氧化应激反应的能力.此外,烟曲霉适应环境及代谢相关的蛋白、通路信号分子、脂类代谢产物、毒素等均可看作毒力因子.