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Determination of Azole Resistance and TR34/L98H Mutations in Isolates of Aspergillus Section Fumigati from Turkish Cystic Fibrosis Patients

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Abstract

Background

Aspergillus fumigatus is the species section Fumigati most frequently isolated from the respiratory tract of cystic fibrosis (CF) patients. Recent studies suggest that mutations in the Cyp51 gene, particularly TR34/L98H, are responsible for azole resistance.

Objectives and Methods

The focus of this study was on section Fumigati isolates isolated from the respiratory tract samples of CF patients. More specifically, the goal was to detect A. fumigatus isolates, test their antifungal susceptibility to itraconazole, voriconazole and posaconazole, and finally determine the presence of TR34/L98H and other mutations in the isolates Cyp51A gene.

Results and Conclusions

A set of 31 isolates of Aspergillus section Fumigati were obtained from the sputum samples of 6 CF patients and subsequently identified to species level by microsatellite genotyping. All isolates were determined as A. fumigatus and involved 14 different genotypes. The minimal inhibitory concentrations to the three azoles were determined by the E-test method, and the Cyp51A gene was sequenced. One of the genotypes was found to be resistant to all azoles but no mutations were detected in the Cyp51A gene, especially the TR34/L98H mutation. Therefore, mutations in genes other than Cyp51A or other distinct mechanisms may be responsible for this reported multiazole resistance found in a Turkish CF patient.

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Acknowledgements

This work was supported by the Research Fund of Istanbul University, Project No. 47641 and Federation of European Microbiological Societies (FEMS) Research Fellowship 2015-0048. i3S was partially financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). As control isolates, itraconazole sensitive (V089-25) and itraconazole resistant (V089-27) isolates obtained from Paul E. Verweij (Radboud University Nijmegen Medical Center) were used.

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Authors and Affiliations

  1. Istanbul Medical Faculty, Department of Medical Microbiology, Istanbul University, 34093, Capa, Istanbul, Turkey

    Özge Güngör & Zayre Erturan

  2. Faculty of Dental Medicine, University of Porto, Porto, Portugal

    Benedita Sampaio-Maia

  3. INEB, Instituto Nacional de Engenharia Biomédica da Universidade do Porto, Porto, Portugal

    Benedita Sampaio-Maia

  4. i3S, Instituto de Investigação e Inovação em Saúde da Universidade do Porto, Porto, Portugal

    Benedita Sampaio-Maia, Antonio Amorim & Ricardo Araujo

  5. Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal

    Antonio Amorim

  6. Faculdade de Ciências, Universidade do Porto, Porto, Portugal

    Antonio Amorim

  7. Department of Medical Biotechnology, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia

    Ricardo Araujo

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  1. Özge Güngör
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Correspondence to Özge Güngör.

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Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors. This study received approval from Istanbul University, Istanbul Medical Faculty, Clinical Research Ethics Committee to be conducted (15.08.2014/1251).

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Handling editor: Patrick CY Woo.

Özge Güngör and Zayre Erturan: Members of the ECMM/ISHAM Working group on Fungal Respiratory Infections in Cystic Fibrosis (Fri-CF).

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Güngör, Ö., Sampaio-Maia, B., Amorim, A. et al. Determination of Azole Resistance and TR34/L98H Mutations in Isolates of Aspergillus Section Fumigati from Turkish Cystic Fibrosis Patients. Mycopathologia 183, 913–920 (2018). https://doi.org/10.1007/s11046-018-0297-y

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  • DOI: https://doi.org/10.1007/s11046-018-0297-y

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