Uncovering a Novel cyp51A Mutation and Antifungal Resistance in Aspergillus fumigatus through Culture Collection Screening
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Published:2024-02-01
Issue:2
Volume:10
Page:122
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ISSN:2309-608X
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Container-title:Journal of Fungi
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language:en
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Short-container-title:JoF
Author:
Pontes Laís1ORCID, Arai Teppei2ORCID, Gualtieri Beraquet Caio Augusto1, Giordano Ana Luisa Perini Leme1, Reichert-Lima Franqueline3, da Luz Edson Aparecido4, Fernanda de Sá Camila4, Ortolan Levy Larissa1, Tararam Cibele Aparecida1, Watanabe Akira2ORCID, Moretti Maria Luiza1, Zaninelli Schreiber Angélica1ORCID
Affiliation:
1. School of Medical Sciences, University of Campinas, Campinas 13083-970, São Paulo, Brazil 2. Division of Clinical Research, Medical Mycology Research Center, Chiba University, Chiba 260-8670, Japan 3. Department of Medicine, School of Medical Sciences in São José dos Campos—Humanitas, São José dos Campos 12220-061, São Paulo, Brazil 4. Division of Clinical Pathology, Microbiology Laboratory, University of Campinas Clinical Hospital, Campinas 13083-888, São Paulo, Brazil
Abstract
Background: Aspergillus fumigatus is an important concern for immunocompromised individuals, often resulting in severe infections. With the emergence of resistance to azoles, which has been the therapeutic choice for Aspergillus infections, monitoring the resistance of these microorganisms becomes important, including the search for mutations in the cyp51A gene, which is the gene responsible for the mechanism of action of azoles. We conducted a retrospective analysis covering 478 A. fumigatus isolates. Methods: This comprehensive dataset comprised 415 clinical isolates and 63 isolates from hospital environmental sources. For clinical isolates, they were evaluated in two different periods, from 1998 to 2004 and 2014 to 2021; for environmental strains, one strain was isolated in 1998, and 62 isolates were evaluated in 2015. Our primary objectives were to assess the epidemiological antifungal susceptibility profile; trace the evolution of resistance to azoles, Amphotericin B (AMB), and echinocandins; and monitor cyp51A mutations in resistant strains. We utilized the broth microdilution assay for susceptibility testing, coupled with cyp51A gene sequencing and microsatellite genotyping to evaluate genetic variability among resistant strains. Results: Our findings reveal a progressive increase in Minimum Inhibitory Concentrations (MICs) for azoles and AMB over time. Notably, a discernible trend in cyp51A gene mutations emerged in clinical isolates starting in 2014. Moreover, our study marks a significant discovery as we detected, for the first time, an A. fumigatus isolate carrying the recently identified TR46/F495I mutation within a sample obtained from a hospital environment. The observed cyp51A mutations underscore the ongoing necessity for surveillance, particularly as MICs for various antifungal classes continue to rise. Conclusions: By conducting resistance surveillance within our institution’s culture collection, we successfully identified a novel TR46/F495I mutation in an isolate retrieved from the hospital environment which had been preserved since 1998. Moreover, clinical isolates were found to exhibit TR34/L98H/S297T/F495I mutations. In addition, we observed an increase in MIC patterns for Amphotericin B and azoles, signaling a change in the resistance pattern, emphasizing the urgent need for the development of new antifungal drugs. Our study highlights the importance of continued monitoring and research in understanding the evolving challenges in managing A. fumigatus infections.
Funder
CAPES (AUXPE) Processo Science and Technology Research Partnership for Sustainable Development (SATREPS), Japan, and University of Campinas, São Paulo, Brazil
Subject
Plant Science,Ecology, Evolution, Behavior and Systematics,Microbiology (medical)
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