• Mycobiology
• /
• v.39 no.1
• /
• pp.40-44
• /
• 2011

Aspergillus fumigatus is associated with invasive disease aspergillosis in immunocompromised individuals. The major aim of this study was to investigate the biochemical and immunological responses of male Wistar rats against A. fumigatus experimentally-induced pulmonary fungal infection. Nostril experimental exposure of male Wistar rats to a high dose of A. fumigatus freeze-dried preparation for only 24 hr resulted in a significant increase in levels of catalase, nitric oxide and lipid peroxide in lung homogenates, compared to those of the control animals. However, the oxidative status of the lungs of rats challenged with killed fungus did not change significantly, except for the stimulation in the level of lipid peroxide. IgG level was significantly elevated only in rats that received two low doses of fungus, compared to unexposed animals (p < 0.005). Examining the lung of rats exposed to A. fumigatus revealed no abnormal changes, except for pus in bronchial lumen spaces and per bronchial inflammation. Histologically, large numbers of granuloma cells were evident in the lungs of challenged rats, while no granuloma formation was evident in the lungs of rats exposed to killed fungus.

• Mycobiology
• /
• v.38 no.4
• /
• pp.229-237
• /
• 2010

Members of the genus Aspergillus are the most common fungi and all reproduce asexually by forming long chains of conidiospores (or conidia). The impact of various Aspergillus species on humans ranges from beneficial to harmful. For example, several species including Aspergillus oryzae and Aspergillus niger are used in industry for enzyme production and food processing. In contrast, Aspergillus flavus produce the most potent naturally present carcinogen aflatoxins, which contaminate various plant- and animal-based foods. Importantly, the opportunistic human pathogen Aspergillus fumigatus has become the most prevalent airborne fungal pathogen in developed countries, causing invasive aspergillosis in immunocompromised patients with a high mortality rate. A. fumigatus produces a massive number of small hydrophobic conidia as the primarymeans of dispersal, survival, genome-protection, and infecting hosts. Large-scale genome-wide expression studies can now be conducted due to completion of A. fumigatus genome sequencing. However, genomics becomes more powerful and informative when combined with genetics. We have been investigating the mechanisms underlying the regulation of asexual development (conidiation) and gliotoxin biosynthesis in A. fumigatus, primarily focusing on a characterization of key developmental regulators identified in the model fungus Aspergillus nidulans. In this review, I will summarize our current understanding of how conidiation in two aspergilli is regulated.

• Tuberculosis and Respiratory Diseases
• /
• v.65 no.5
• /
• pp.400-404
• /
• 2008

Aspergillus tracheobronchitis (ATB), a variant of invasive pulmonary aspergillosis, is characterized by extensive tracheobronchitis and pseudomembrane formation. ATB usually occurs in immunocompromised patients with a high fatality rate. We report a case of ATB in a previously healthy patient who responded well to antifungal therapy.

• Journal of Microbiology and Biotechnology
• /
• v.14 no.1
• /
• pp.74-80
• /
• 2004

Aspergillus fumigatus is one of the most common fungi in the human environment, both in-doors and out-doors. It is the main causative agent of invasive aspergillosis, a life-threatening mycosis among immunocompromised patients. The genome has been sequenced by an international consortium, including the Wellcome Trust Sanger Institute (U.K.) and The Institute for Genomic Research (TIGR, U.S.A.), and a ten times whole genome shotgun sequence assembly has been made publicly available. In this study, we identified tricarboxylic acid (TCA) cycle enzymes of A. fumigatus by comparative analysis with four other fungal species. The open reading frames showed high amino acid sequence similarity with the other fungal citric acid enzymes and well-conserved functional domains. All genes present in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans, and Neurospora crassa were also found in A. fumigatus. In addition, we identified four A. fumigatus genes coding for enzymes in the glyoxylate shunt, which may be required for fungal virulence. The architecture of multi-gene encoded enzymes, such as isocitrate dehydrogenase, 2-ketoglutarate, succinyl-CoA synthetase, and succinate dehydrogenase was well conserved in A. fumigatus. Furthermore, our results show that genes of A. fumigatus can be detected reliably using GlimmerM.

• Journal of Veterinary Clinics
• /
• v.15 no.1
• /
• pp.180-183
• /
• 1998

A 5 year-old male Throughbred horse housed in Korean Racing Association died after having enteritis and respiratory disorder for about 10 days. At necropsyi the left and right caudal lung lobes were reddenedi swolleni and contained numerous well-defined sublobular consolidated foci. The large intestine was diffusely reddened and covered with pseudomembranous exudates. Microscopicallyi multifocal areas of necrosis with mild to moderate infiltration of neutrophilsi macrophages and Iymphocytes as well as hemorrhage and edema were noted in the lung. The fungi having conidiophorei dome-shaped vesicles phialides and conidia which are characteristic of Apergillosis fumigatus was isolated from the lung. The colonic mucosa was transmurally necrotic and severe congestions edema and thrombi were observed in the submucosa. The embolic mycotic pneumonia present in this case Probably occured secondary to antibiotic therapy given for treatment of enteritis.

• Korean Journal of Microbiology
• /
• v.19 no.3
• /
• pp.142-152
• /
• 1981

One hundred and thirteen healed pulmonary tuberculosis patients and 11 patients with other underlying diseases were studied for evidence of pulmonary fungal infection because of persisting hemoptysis or chronic cough. Rediological, mycological and serological investigations revealed that 54 out of 124 patients were evidently infected with one or more species of fungi. A. fumigatus was isolated from 4 out of 70 patients whose sera did not react with antigens from this fungus, while it was isolated from 43 out of 47 serological reactors to this fungus. Chest radiography showed a distinct fungus ball in a cyst of one patient and in a preformed cavity in the lung of 17 healed tuberculosis patients and two other patients. The latter two patients were infected with A.flavus. Two patients, who were under the long period of immunosuppressive therapy, apparently succumbed to invasive aspergillosia due to A.fumigatus. A single or dual infection with A. flavus, A. nidulans, A.nidulans var. latus, C. albicans, and P. boydii were noticed in some patients without mycetomal shadow on chest radiographs. Young mycelial extract (ME) of A.fumigatus detected antibody in 95.8 percent of the sera from patients infected with this fungus, while it was isolated from 43 out of 47 serological reactors to this fungus. Chest radiography showed a distinct fungus ball in a cyst of one patient and in a performed cavity in the lung of 17 healed tuberculosis patients and two other patients. The latter two patients were infected with A. flavus. Two patients, who were under the long period of immunosuppressive therapy, apparently succumbed to invasive aspergillosis due to A.fumigatus. A single or dual infection with A. flavus, A. nidulans, A. niduans var. latus, C. albicans, and P. boydii were noticed in some patients without mycetomal shadow on chest radiographs. Young mycelial extract (ME) of A.fumigatus detected antibody in 95.8 percent of the sera from patients infected with this fungus, while the commercial culture filtrate antigen (GL) yielded 78.7 per cent positive result. Culture filtrate antigen, however, was comparable with ME. There was no single antigen with which all the serum specimens reacted. Fractionation of ME resulted in a loss of some activity although it excluded substances that reacted with C-reactive protein in a loss of some activity although it excluded substances that reacted with C-reactive protein. Most reactive and specific precipitinogens distributed in the fraction (FB) which was precipitable at 75 percent saturation with ammonium sulfate and eluted in a second peak in order from gel-filtration and which contained mostly proteinic components. Glycoproteins or polysaccharides rich fractions (FA and ASI) were relatively less effective in detecting antibody. Demonstration of antibody in the serum from patients using a battery of fungal antigens and of etiologically related fungi from clinical specimens are very useful laboratory procedures for the diagnosis of pulmonary fungal infection which is a common complication of tuberculosis.

• Pediatric Infection and Vaccine
• /
• v.21 no.1
• /
• pp.9-21
• /
• 2014

Purpose: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. Methods: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012 were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patients were assessed for adverse events and treatment response six weeks into treatment, and at the end. Results: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading (6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverse events occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-related encephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1 %) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within the therapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events was lower in the TDM group (0.0% vs. 18.2%, P =0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in the non-TDM group showed clinical response after 6 weeks (P =0.055), whereas 21.4% in the TDM group versus 14.3% in the non-TDM group showed response at final outcome (P =0.664). In the TDM group, >67.0% of the serum levels were within therapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. Conclusion: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.

• 한국균학회소식:학술대회논문집
• /
• 2015.05a
• /
• pp.15-15
• /
• 2015

Aspergillus fumigatus is a major cause of invasive aspergillosis (IA), a significant health issue worldwide with high mortality rates up to 95%. Our lab is interested in how A. fumigatus adapts to low oxygen conditions 'hypoxia', which is one of the important host microenvironments. A. fumigatus SrbA is a basic helix-loop-helix (bHLH) transcriptional regulator and belongs to sterol regulatory element binding protein (SREBP) family members. Loss of SrbA completely blocks growth in hypoxia and results in avirulence in murine models of IA suggesting an essential role of SrbA in hypoxia adaptation and virulence in A. fumigatus. We conducted chromatin immunoprecipitation sequencing (ChIP-seq) with A. fumigatus wild type using a SrbA specific antibody, and 97 genes were revealed as SrbA direct targets. One of the 'SrbA regulons' (AFUB_099590) was a putative bHLH transcriptional regulator whose sequence contained a characteristic tyrosine substitution in the basic portion of the bHLH domain of SREBPs. Therefore, we designated AFUB_099590 SrbB. Further characterization of SrbB demonstrated that SrbB is important for radial growth, biomass production, and biosynthesis of heme intermediates in hypoxia and virulence in A. fumigatus. A series of quantitative real time PCR showed that transcription of several SrbA regulons is coordinately regulated by two SREBPs, SrbA and SrbB in hypoxia. This suggests that SrbA and SrbB have both dependent and independent functions in regulation of genes responsible for hypoxia adaptation in A. fumigatus. Together, our data provide new insights into complicated roles of SREBPs in adaptation of host environments and virulence in pathogenic fungi.

• Tuberculosis and Respiratory Diseases
• /
• v.47 no.2
• /
• pp.209-217
• /
• 1999

Backgrounds: To investigate the role of CT as a screening tool and to compare the diagnostic accuracy with that of the fiberoptic bronchoscopy (FOB) in evaluating the causes of hemoptysis. Methods: The retrospective review of plain chest radiograph, CT and FOB was done in 72 patients with hemoptysis. The diagnosis were confirmed by histology (n=33), bacterial culture (n=6), cytology (n=3), serology (n=2), skin test (n= 1), clinical response (n=5), and airway disease mainly by HRCT (n=22). Results: The causes of hemoptysis were shown to be lung cancer (n=29), bronchiectasis (n=19), tuberculosis (n=12), aspergilloma (n=5), invasive aspergillosis (n=l), COPD (n=3) and others (n=3). The sensitivity was 100% and 91,7% by CT and FOB respectively. The diagnostic compatibility was 95.8% and 59.7% by CT and FOB respectively. The diagnostic compatibility in cases with central airway disease was 96.3% and 100 % in CT and FOB. In parenchymal disease, CT and FOB showed 91.3 % and 43.5 % of compatibility, respectively. airway disease, CT and FOB showed 100% and 31.8% compatibility, respectively. That is to say, CT has higher sensitivity and diagnostic compatibility than FOB for identifying the causes of hemoptysis, and is more helpful for patients with hemoptysis from parenchymal or airway disease. FOB had the advantage in obtaining histologic, cytologic and bacteriologic diagnosis with biopsy or washing Conclusion: CT should be used as the screening method before performing FOB for patients with hemoptysis who have normal or nonspecific findings or peripheral airway disease in plain chest radiograph.