A novel combination of CYP51A mutations confers pan-azole resistance in Aspergillus fumigatus.

A novel combination of CYP51A mutations confers pan-azole resistance in Aspergillus fumigatus. Antimicrob Agents Chemother. 2020 May 18;: Authors: Macedo D, Brito Devoto T, Pola S, Finquelievich JL, Cuestas ML, García-Effron G Abstract The treatment of invasive and chronic aspergillosis involves triazole drugs. Its intensive use has resulted in the selection of resistant isolates and at present, azole resistance in Aspergillus fumigatus is considered an emerging threat to public health worldwide.The aim of this work is to uncover the molecular mechanism implicated in the azole resistance phenotype of three Aspergillus fumigatus clinical strains isolated from an Argentinian cystic fibrosis patient under long-term triazole treatment.Strain susceptibilities were assessed and CYP51A gene sequences were analyzed. Two of the studied Aspergillus fumigatus strains harbored the TR34-L98H allele. These strains showed high MIC values for all tested triazole (>16.00 μg/ml, 1.00 μg/ml, 1.00 μg/ml and 2.00 μg/ml for itraconazole, isavuconazole, posaconazole and voriconazole, respectively). The third one showed a novel amino acid change (R65K) combined with the TR34-L98H mutations. This new mutation combination induces a pan-azole MIC augment when compared with TR34-L98H mutants (>16 μg/ml, 4.00 μg/ml, 4.00 μg/ml and 8.00 μg/ml for itraconazole, isavuconazole, posaconazole and voriconazole, respectively). The strain harboring the TR...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research

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Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease that occurs in approximately 9% of children with cystic fibrosis (CF) [1]. While ABPA is commonly associated with worsening lung function, differentiating ABPA from other causes of pulmonary function decline often poses a clinical challenge. This is reflected by major differences among the various diagnostic criteria for ABPA that have been suggested to date [2–5]. A positive bronchodilator response (BDR) is characteristic for asthma which is a common co-morbidity in CF patients, but whether this is helpful in differentiating ABPA from ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Original Articles: Research letters Source Type: research
CONCLUSION: ABPA is recognized as the most common Aspergillus associated disorder in CF patients and is related to deteriorated pulmonary function tests; however Aspergillus colonization and bronchitis may also be associated with worsening lung function. PMID: 32779408 [PubMed - in process]
Source: The Turkish Journal of Pediatrics - Category: Pediatrics Authors: Tags: Turk J Pediatr Source Type: research
Allergic bronchopulmonary aspergillosis (ABPA) is a severe hypersensitivity reaction to aspergillus species colonizing the airways of patients with asthma or cystic fibrosis. Biologics including anti-IgE and a...
Source: Allergy, Asthma and Clinical Immunology - Category: Allergy & Immunology Authors: Tags: Case report Source Type: research
Conference abstracts
Source: The Aspergillus Website - updates - Category: Respiratory Medicine Authors: Source Type: news
Abstract Allergic bronchopulmonary aspergillosis (ABPA) is an inflammatory disease caused by immunologic reactions initiated against Aspergillus fumigatus colonizing the airways of patients with asthma and cystic fibrosis. The common manifestations include treatment-resistant asthma, transient and fleeting pulmonary opacities and bronchiectasis. It is believed that globally there are about five million cases of ABPA, with India alone accounting for about 1.4 million cases. The occurrence of ABPA among asthmatic patients in special clinics may be as high as 13 per cent. Thus, a high degree of suspicion for ABPA sho...
Source: Indian J Med Res - Category: Research Authors: Tags: Indian J Med Res Source Type: research
Purpose of review Aspergillus spp. cause a clinical spectrum of disease with severity of disease dependent on degree of immune compromise, nature and intensity of inflammatory host response, and/or underlying lung disease. Chronic pulmonary aspergillosis encompasses a spectrum of diseases including aspergilloma, Aspergillus nodules, chronic cavitary pulmonary aspergillosis, chronic fibrosing pulmonary aspergillosis, and subacute invasive pulmonary aspergillosis. Allergic bronchopulmonary aspergillosis (ABPA) paradoxically is an immune hypersensitivity manifestation in the lungs that almost always occurs in the setting of...
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: PULMONOLOGY: Edited by David N. Cornfield Source Type: research
Authors: Kaur P, Kumar P, Randev S, Guglani V Abstract Allergic bronchopulmonary aspergillosis (ABPA) is an immunological disease complicating asthma or cystic fibrosis. An 8-year-old girl with no previous respiratory morbidity was diagnosed with ABPA on the basis of a raised eosinophil count and total and specific serum IgE levels combined with a positive skin-prick test for aspergillus and typical CT images of finger-in-glove hilar opacities and hyperattenuating mucous. She responded to treatment with itraconazole and corticosteroids and remains well. As far as we are aware, she is only the second child to be dia...
Source: Paediatrics and international child health - Category: Pediatrics Tags: Paediatr Int Child Health Source Type: research
Aspergillus spp. is a ubiquitous mold found commonly in our environment that can cause a spectrum of pulmonary disorders ranging from a hypersensitivity reaction to an acutely invasive disease with significant mortality. Allergic bronchopulmonary aspergillosis results from airway hypersensitivity from aspergillus colonization almost exclusively in patients with asthma and cystic fibrosis. Chronic pulmonary aspergillosis typically present in immunocompetent patients with underlying lung pathology.
Source: The American Journal of Medicine - Category: General Medicine Authors: Tags: Review Source Type: research
Nurhayat Yakut, Eda Kepenekli Kadayifci, Ela Erdem Eralp, Yasemin GokdemirLung India 2020 37(2):161-163 Allergic bronchopulmonary aspergillosis (ABPA) is recognized as a rare, progressive, allergic disorder in patients with cystic fibrosis (CF) and asthma. Treatment of ABPA mainly includes systemic corticosteroids (CSs) and antifungal agents. Here, we report posaconazole treatment in a 9-year-old male child with ABPA and also review the literature on antifungal management of ABPA. The child with CF was admitted to the emergency room with complaints of fever, productive cough, and acute dyspnea. Auscultation of the lungs r...
Source: Lung India - Category: Respiratory Medicine Authors: Source Type: research
Conclusion: We conclude that basophil and lymphocyte activation tests could enhance the diagnosis of allergic mycosis, compared to usual humoral markers. Further studies with larger cohorts and addressing both mold extracts and mold relevant molecules are needed in order to confirm and extend the application of this personalized medicine approach.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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