Dataset Information

In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR₁₂₀) in Aspergillus fumigatus cyp51A, Denmark.

ABSTRACT: We report a fatal aspergillosis case in which STRAf typing and whole-genome sequencing substantiated in vivo emergence of an azole-resistant Aspergillus fumigatus with a 120-bp tandem repeat in the promoter region of cyp51A. This event, previously restricted to the environment, challenges current understanding of azole resistance development in A. fumigatus.

SUBMITTER: Hare RK

PROVIDER: S-EPMC6390761 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR<sub>120</sub>) in Aspergillus fumigatus cyp51A, Denmark.

Hare Rasmus K RK Gertsen Jan B JB Astvad Karen M T KMT Degn Kristine B KB Løkke Anders A Stegger Marc M Andersen Paal S PS Kristensen Lise L Arendrup Maiken C MC

Emerging infectious diseases 20190301 3

We report a fatal aspergillosis case in which STRAf typing and whole-genome sequencing substantiated in vivo emergence of an azole-resistant Aspergillus fumigatus with a 120-bp tandem repeat in the promoter region of cyp51A. This event, previously restricted to the environment, challenges current understanding of azole resistance development in A. fumigatus. ...[more]

PMID: 30789127

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Project description:Azole-resistant (azole-R) Aspergillus is an increasing challenge worldwide. Patients with cystic fibrosis (CF) are at risk of Aspergillus colonization and disease due to a favorable lung environment for microorganisms. We performed a nationwide study in 2018 of azole-non-susceptible Aspergillus in CF patients and compared with data from two prior studies. All airway samples with mold isolates from patients monitored at the two CF centers in Denmark (RH, Jan-Sept and AUH, Jan-Jun) were included. Classical species identification (morphology and thermo-tolerance) was performed and MALDI-TOF/β-tubulin sequencing was performed if needed. Susceptibility was determined using EUCAST E.Def 10.1, and E.Def 9.3.2. cyp51A sequencing and STRAf genotyping were performed for azole-non-susceptible isolates and relevant sequential isolates. In total, 340 mold isolates from 159 CF patients were obtained. The most frequent species were Aspergillus fumigatus (266/340, 78.2%) and Aspergillus terreus (26/340, 7.6%). Azole-R A. fumigatus was cultured from 7.3% (10/137) of patients, including 9.5% (9/95) of patients at RH and 2.4% at AUH (1/42), respectively. In a 10-year perspective, azole-non-susceptibility increased numerically among patients at RH (10.5% in 2018 vs 4.5% in 2007-2009). Cyp51A resistance mechanisms were found in nine azole-R A. fumigatus from eight CF patients. Five were of environmental origin (TR34/L98H), three were human medicine-driven (two M220K and one M220R), and one was novel (TR34 3/L98H) and found in a patient who also harbored a TR34/L98H isolate. STRAf genotyping identified 27 unique genotypes among 45 isolates and ≥2 genotypes in 8 of 12 patients. This included one patient carrying two unique TR34/L98H isolates, a rare phenomenon. Genotyping of sequential TR34 3/L98H and TR34/L98H isolates from the same patient showed only minor differences in 1/9 markers. Finally, azole-R A. terreus was found in three patients including two with Cyp51A alterations (M217I and G51A, respectively). Azole-R A. fumigatus is increasing among CF patients in Denmark with the environmentally associated resistance TR34/L98H mechanism being dominant. Mixed infections (wildtype/non-wildtype and several non-wildtypes) and a case of potential additional tandem repeat acquisition in vivo were found. However, similar genotypes were identified from another patient (and outside this study), potentially suggesting a predominant TR34/L98H clone in DK. These findings suggest an increasing prevalence and complexity of azole resistance in A. fumigatus.

Dataset Information

In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR₁₂₀) in Aspergillus fumigatus cyp51A, Denmark.

Publications

In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR<sub>120</sub>) in Aspergillus fumigatus cyp51A, Denmark.

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Dataset Information

In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR120) in Aspergillus fumigatus cyp51A, Denmark.

Publications

In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR<sub>120</sub>) in Aspergillus fumigatus cyp51A, Denmark.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

In Vivo Selection of a Unique Tandem Repeat Mediated Azole Resistance Mechanism (TR₁₂₀) in Aspergillus fumigatus cyp51A, Denmark.