scholarly journals An unusual clinical isolate of Aspergillus fumigatus Series from a patient with fungus ball in a cystic change

1981 ◽  
Vol 28 (2) ◽  
pp. 70-74
Author(s):  
Sang Jae Kim ◽  
Chung Hee Lee ◽  
Yung Rak Chung
Keyword(s):  
Aspergillus Fumigatus ◽  
Clinical Isolate ◽  
Fungus Ball ◽  
Cystic Change

Point mutation or overexpression of A. fumigatus cyp51B, encoding lanosterol 14α-sterol demethylase, leads to triazole resistance.

2021 ◽  
Author(s):  
Mariana Handelman ◽  
Zohar Meir ◽  
Jennifer Scott ◽  
Yona Shadkchan ◽  
Wei Liu ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Point Mutation ◽  
Clinical Isolate ◽  
Recipient Strain ◽  
Antifungal Treatment ◽  
Ergosterol Biosynthesis ◽  
Common Cause ◽  
Clinical Resistance

Aspergillus fumigatus is the most common cause of invasive fungal mold infections in immunocompromised individuals. Current antifungal treatment relies heavily on the triazole antifungals which inhibit fungal Erg11/Cyp51 activity and subsequent ergosterol biosynthesis. However, resistance, due primarily to cyp51 mutation, is rapidly increasing. A. fumigatus contains two Cyp51 isoenzymes, Cyp51A and Cyp51B. Overexpression and mutation of Cyp51A is a major cause of triazole resistance in A. fumigatus . The role of Cyp51B in generating resistance is unclear. Here we show that overexpression or mutation of cyp51B results in triazole resistance. We demonstrate that introduction of a G457S Cyp51B mutation identified in a resistant clinical isolate, results in voriconazole resistance in the naïve recipient strain. Our results indicate that mutations in cyp51B resulting in clinical resistance do exist and should be monitored.

scholarly journals Endocytic Markers Associated with the Internalization and Processing of Aspergillus fumigatus Conidia by BEAS-2B Cells

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Helen R. Clark ◽  
Allison B. Powell ◽  
Kelsey A. Simmons ◽  
Tariq Ayubi ◽  
Shiv D. Kale
Keyword(s):  
Epithelial Cells ◽  
Aspergillus Fumigatus ◽  
Clinical Isolate ◽  
Airway Epithelial Cells ◽  
Epithelial Cell Line ◽  
Initial Contact ◽  
Airway Epithelial ◽  
Class Iii ◽  
Content Type ◽  
Therapeutic Development

ABSTRACT Aspergillus fumigatus is a ubiquitous mold that produces small airborne conidia capable of traversing deep into the respiratory system. Recognition, processing, and clearance of A. fumigatus conidia by bronchial airway epithelial cells are thought to be relevant to host defense and immune signaling. Using z-stack confocal microscopy, we observed that only 10 to 20% of adherent conidia from the AF293 clinical isolate are internalized by BEAS-2B cells 6 h postchallenge and not prior. Similar percentages of internalization were observed for the CEA10 clinical isolate. A large subset of both AF293 and CEA10 conidia are rendered metabolically inactive without internalization at 3 h postchallenge by BEAS-2B cells. A significantly larger percentage of CEA10 conidia are metabolically active at 9 and 12 h postchallenge in comparison to the AF293 isolate, demonstrating heterogeneity among clinical isolates. We identified 7 host markers (caveolin, flotillin-2, RAB5C, RAB8B, RAB7A, 2xFYVE, and FAPP1) that consistently localized around internalized conidia 9 h postchallenge. Transient gene silencing of RAB5C, PIK3C3, and flotillin-2 resulted in a larger population of metabolically active conidia. Our findings emphasize the abundance of both host phosphatidylinositol 3-phosphate (PI3P) and PI4P around internalized conidia, as well as the importance of class III PI3P kinase for conidial processing. Therapeutic development focused on RAB5C-, PIK3C3-, and flotillin-2-mediated pathways may provide novel opportunities to modulate conidial processing and internalization. Determination of how contacted, external conidia are processed by airway epithelial cells may also provide a novel avenue to generate host-targeted therapeutics. IMPORTANCE Conidia from the fungus Aspergillus fumigatus are notorious for their ability to stay airborne. This characteristic is believed to allow conidia to penetrate into the cleanest environments. Several hundred conidia are thought to be inhaled each day by a given individual and then expelled by mucociliary clearance. Given that airway epithelial cells make up a significant portion of the pulmonary-air interface, we set out to determine the percentage of conidia that are actually internalized after initial contact with airway epithelial cells. We determined this through an in vitro assay using an immortalized bronchial airway epithelial cell line known as BEAS-2B. Our results suggest a small fraction of conidia are internalized by BEAS-2B cells, while the majority stay adherent to the surface of cells or are washed away during sample processing. Internalization of conidia was observed at 6 h postchallenge and not prior. Our data also indicate conidia are rendered metabolically inactive within 3 h of challenge, suggesting BEAS-2B cells process a large number of conidia without internalization in this early time frame. We have also identified several host endocytosis markers that localize around internalized conidia as well as contribute to the processing of conidia. Understanding how these host endocytosis markers affect the processing of internal and/or external conidia may provide a novel avenue for therapeutic development.

scholarly journals Molecular Identification of a Clinical Isolate of Non-pigmented and Asporogenic Aspergillus fumigatus Strain Which cannot be Identified by Traditional Morphological Methods.

2001 ◽  
Vol 42 (2) ◽  
pp. 91-93 ◽  
Author(s):  
Kayo Watanabe ◽  
Masakazu Katsu ◽  
Miki Tamura ◽  
Katsukiyo Yazawa ◽  
Katsuhiko Kamei ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Clinical Isolate ◽  
Molecular Identification

scholarly journals Effect of N-chlorotaurine on Aspergillus, with particular reference to destruction of secreted gliotoxin

2006 ◽  
Vol 55 (7) ◽  
pp. 913-918 ◽  
Author(s):  
Emer P. Reeves ◽  
Markus Nagl ◽  
Joseph O'Keeffe ◽  
Judy Kelly ◽  
Kevin Kavanagh
Keyword(s):  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Clinical Isolate ◽  
Topical Treatment ◽  
Therapeutic Efficacy ◽  
Fungicidal Activity ◽  
Immunosuppressive Agent ◽  
Good Choice ◽  
Disulphide Bridge ◽  
High Antifungal Activity

The fungistatic and fungicidal activity of N-chlorotaurine (NCT), a long-lived oxidant produced by stimulated neutrophils, was investigated. Physiological concentrations (75–100 μM) of NCT showed clear fungicidal activity against a range of Aspergillus isolates. Moreover, killing by NCT was significantly increased in the presence of ammonium chloride, explained by the formation of monochloramine by halogenation of ammonium. One clinical isolate of Aspergillus fumigatus was characterized for the production of the immunosuppressive agent gliotoxin, and NCT was shown to cause destruction of gliotoxin, possibly via reduction of the disulphide bridge. Because of its endogenous nature and its high antifungal activity, NCT appears to be a good choice for topical treatment of Aspergillus infections, and the results of this study further substantiate its therapeutic efficacy.

scholarly journals Clinical and experimental phenotype of azole-resistant Aspergillus fumigatus with a HapE splice site mutation: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuya Ito ◽  
Takahiro Takazono ◽  
Satoru Koga ◽  
Yuichiro Nakano ◽  
Nobuyuki Ashizawa ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Splice Site ◽  
Splice Site Mutation ◽  
Antifungal Treatment ◽  
Resistant Isolate ◽  
Infection Model ◽  
Low Grade ◽  
Fungus Ball ◽  
Site Mutation

Abstract Background The recent increase in cases of azole-resistant Aspergillus fumigatus (ARAf) infections is a major clinical concern owing to its treatment limitations. Patient-derived ARAf occurs after prolonged azole treatment in patients with aspergillosis and involves various cyp51A point mutations or non-cyp51A mutations. The prognosis of patients with chronic pulmonary aspergillosis (CPA) with patient-derived ARAf infection remains unclear. In this study, we reported the case of a patient with ARAf due to HapE mutation, as well as the virulence of the isolate. Case presentation A 37-year-old male was presented with productive cough and low-grade fever. The patient was diagnosed with CPA based on the chronic course, presence of a fungus ball in the upper left lobe on chest computed tomography (CT), positivity for Aspergillus-precipitating antibody and denial of other diseases. The patient underwent left upper lobe and left S6 segment resection surgery because of repeated haemoptysis during voriconazole (VRC) treatment. The patient was postoperatively treated with VRC for 6 months. Since then, the patient was followed up without antifungal treatment but relapsed 4 years later, and VRC treatment was reinitiated. Although an azole-resistant isolate was isolated after VRC treatment, the patient did not show any disease progression in either respiratory symptoms or radiological findings. The ARAf isolated from this patient showed slow growth, decreased biomass and biofilm formation in vitro, and decreased virulence in the Galleria mellonella infection model compared with its parental strain. These phenotypes could be caused by the HapE splice site mutation. Conclusions This is the first to report a case demonstrating the clinical manifestation of a CPA patient infected with ARAf with a HapE splice site mutation, which was consistent with the in vitro and in vivo attenuated virulence of the ARAf isolate. These results imply that not all the ARAf infections in immunocompetent patients require antifungal treatment. Further studies on the virulence of non-cyp51A mutations in ARAf are warranted.

scholarly journals Fungus ball in HIV-infected patients

2009 ◽  
Vol 51 (6) ◽  
pp. 345-348 ◽  
Author(s):  
Luciana Silva Guazzelli ◽  
Gisela Unis ◽  
Melissa Orzechowski Xavier ◽  
Cecília Bittencourt Severo ◽  
Pedro Dornelles Picon ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Lung Disease ◽  
Radiographic Feature ◽  
Fungus Ball ◽  
Fungal Ball

Aspergillus is a phagocyte opportunistic fungus that causes aspergillosis, an unusual disease in patients with AIDS. Six cases of fungal ball in patients with AIDS are reported here. In this group, all patients had hemoptysis and tuberculosis as the underlying lung disease. The diagnosis of pulmonary fungus ball was based on the clinical and radiographic feature, combined with serological and mycological evidence of Aspergillus fumigatus.

scholarly journals Aspergillus fumigatus fungus ball in hospitalized patients with chronic pulmonary disease: usefulness of double immunodiffusion test as a screening procedure

1988 ◽  
Vol 83 (3) ◽  
pp. 357-360 ◽  
Author(s):  
M. F. Ferreira-da-Cruz ◽  
B. Wanke ◽  
C. Pirmez ◽  
B. Galvão-Castro
Keyword(s):  
Aspergillus Fumigatus ◽  
Clinical History ◽  
Pathological Examination ◽  
Fungus Ball ◽  
X Rays ◽  
Double Immunodiffusion ◽  
Positive Serology ◽  
Radiographic Findings ◽  
Chest Disease ◽  
Considerable Problem

Double immunodiffusion (DID) was used as a screening test for the diagnosis of aspergillosis. Three hundred and fifty patients were tested, all of them referred from a specialized chest disease hospital and without a definitive etiological diagnosis. When DID was positive addtional information such as clinical history and radiographic findings were requested and also surgical specimens were obtained whenever possible. Specific precipitin hamds for Aspergillus fumigatus antigen were found in 29 (8.3%) of 350 patients sera. Nineteen (65.5%) of the 29 patients with positive serology were recognized as having a fungus ball by X-rays signs in 17 or by pathological examination in 2 or by both in 8 patients. This two-year prospective study has shown that pulmonary aspergillos is a considerable problem among patiens admitted to a Chest Diseases Hospital, especially in those with pulmonary cavities or bronchiectasis.

First itraconazole resistant Aspergillus fumigatus clinical isolate harbouring a G54E substitution in Cyp51Ap in South America

2017 ◽  
Vol 34 (1) ◽  
pp. 46-48 ◽  
Author(s):  
Florencia Leonardelli ◽  
Laura Theill ◽  
María Elena Nardin ◽  
Daiana Macedo ◽  
Catiana Dudiuk ◽  
...  
Keyword(s):  
South America ◽  
Aspergillus Fumigatus ◽  
Clinical Isolate

Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate

2002 ◽  
Vol 36 (3) ◽  
pp. 199-206 ◽  
Author(s):  
John W Slaven ◽  
Michael J Anderson ◽  
Dominique Sanglard ◽  
Graham K Dixon ◽  
Jacques Bille ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Clinical Isolate ◽  
Abc Transporter ◽  
Transporter Gene
Sign in / Sign up

Export Citation Format

Share Document