Special Issue "Azole Resistance in Aspergillus spp."

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Genomics, Genetics and Molecular Biology".

Deadline for manuscript submissions: 31 March 2023 | Viewed by 1790

Special Issue Editors

Dr. Teresa Peláez
E-Mail Website
Guest Editor
1. Microbiology Department, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain
2. Biosanitary Foundation for Research in the Principality of Asturias (FINBA), 33011 Oviedo, Spain
Interests: mycological diagnosis; antifungal resistance; antifungal tolerance; clinical implication of antifungal resistance; azole resistance in the environment
Dr. Clara Valero
E-Mail Website
Guest Editor
Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility, Manchester, UK
Interests: Aspergillus molecular biology; antifungal resistance; antifungal tolerance; Aspergillus stress response

Special Issue Information

Dear Colleagues,

Aspergillus spp. fungi affect millions of patients and cause hundreds of thousands of life-threatening infections every year. Azoles have been used for many years as the main antifungal agent to treat and prevent Aspergillus spp. infections. However, these organisms can develop azole resistance in certain environments when exposed to azole compounds used as fungicides or during the long-term treatment of patients with chronic infections. Azole resistance can be devastating as almost 90% of invasive aspergillosis patients infected with a drug-resistant strain die, while chronic patients with resistant infections are administered treatments that are either poorly tolerated or less efficacious. Furthermore, some isolates show the remarkable ability to tolerate azole concentrations greater than the minimal inhibitory concentration, which may also impact clinical outcomes and act as a precursor of azole resistance. Thus, azole resistance poses a significant threat to human health with important economic implications.

This Special Issue is dedicated to Aspergillus spp. azole resistance. Among other topics, it will cover the important research and innovation needed to implement risk reduction strategies that can minimize the emergence of resistance and improve disease management.

Sincerely,

Dr. Teresa Peláez
Dr. Clara Valero
Guest Editors

Manuscript Submission Information

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Keywords

  • azole resistance molecular mechanisms
  • clinical azole resistance
  • environmental azole resistance
  • evolution of azole resistance
  • detection of azole resistance
  • azole tolerance/persistence

Published Papers (2 papers)

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Research

Article
Quantitative PCR Effectively Quantifies Triazole-Susceptible and Triazole-Resistant Aspergillus fumigatus in Mixed Infections
J. Fungi 2022, 8(11), 1120; https://doi.org/10.3390/jof8111120 - 25 Oct 2022
Cited by 1 | Viewed by 713
Abstract
Increasing resistance to triazole antifungals in Aspergillus fumigatus is worrisome because of the associated high mortality of triazole-resistant A. fumigatus (TRAF) infections. While most studies have focused on single triazole-susceptible (WT) or TRAF infections, reports of TRAF cases developing mixed WT and TRAF [...] Read more.
Increasing resistance to triazole antifungals in Aspergillus fumigatus is worrisome because of the associated high mortality of triazole-resistant A. fumigatus (TRAF) infections. While most studies have focused on single triazole-susceptible (WT) or TRAF infections, reports of TRAF cases developing mixed WT and TRAF infections have been described in several studies. However, the prevalence of mixed infections and their responses to current recommended therapies are unknown and could be inappropriate, leading to poor clinical outcomes. To address the urgent need for tools to diagnose, monitor disease development and therapy efficacies in mixed infection settings where quantification of WT versus TRAF is key, this study developed a novel qPCR assay to differentiate WT and TRAF harboring the cyp51A-TR34/L98H mutation. The proposed assay successfully quantified A. fumigatus and discriminated TRAF-TR34 in vitro and in vivo, which was achieved by increasing the yield of extracted DNA through improved homogenization and specific primers targeting the WT-sequence or TR34-insertion and a TaqMan-probe directed to A. fumigatus. The here-developed qPCR assay overcomes sensitivity issues of methodologies such as CFU counts, providing specific, reproducible, and reliable quantitative information to study and follow up the (interplay and individual) effects of mixed A. fumigatus infections on disease development and treatment responses. Full article
(This article belongs to the Special Issue Azole Resistance in Aspergillus spp.)
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Article
Azole Resistance and cyp51A Mutation of Aspergillus fumigatus in a Tertiary Referral Hospital in Taiwan
J. Fungi 2022, 8(9), 908; https://doi.org/10.3390/jof8090908 - 26 Aug 2022
Cited by 1 | Viewed by 824
Abstract
Azole resistance in Aspergillus fumigatus has increasingly been reported worldwide. Its major mechanism of resistance is mediated by mutations in cyp51A. The objective of this study was to test the antifungal susceptibilities of A. fumigatus isolates from Chang Gung Memorial Hospital (CGMH), [...] Read more.
Azole resistance in Aspergillus fumigatus has increasingly been reported worldwide. Its major mechanism of resistance is mediated by mutations in cyp51A. The objective of this study was to test the antifungal susceptibilities of A. fumigatus isolates from Chang Gung Memorial Hospital (CGMH), the largest tertiary referral hospital in Taiwan, and to investigate cyp51A mutations in azole-resistant strains. A. fumigatus isolates preserved in the Research Laboratory of Medical Mycology of CGMH from 2015 to 2021 were used. Antifungal susceptibility testing was performed using the YeastOneTM method. Isolates with high minimal inhibitory concentrations (MICs) against antifungals were further tested using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Mutations in the cyp51A in azole-resistant strains were detected by Sanger sequencing. The overall prevalence of azole-resistant isolates was 1.77% (two out of 113 isolates). The two azole-resistant strains had tandem repeats (TR) in the promoter region and mutations in the cyp51A gene (TR34/L98H and TR34/L98H/S297T/F495I). One strain showed intermediate susceptibility to voriconazole, and its Cyp51A protein had five amino acid substitutions (F46Y/M172V/N248T/D255E/E427K). TR34/L98H and TR34/L98H/S297T/F495I are the most prevalent cyp51A mutations in Taiwan, mediating azole resistance based on current publications and our results. YeastOneTM was validated as a rapid tool for the antifungal susceptibility test; however, further confirmation by CLSI should be considered when MIC values of voriconazole, posaconazole, and amphotericin B are close to the clinical breakpoints or ecological cutoff values. Full article
(This article belongs to the Special Issue Azole Resistance in Aspergillus spp.)
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