Molecular Identification, Antifungal Susceptibility Testing, and Mechanisms of Azole Resistance in
            <i>Aspergillus</i>
            Species Received within a Surveillance Program on Antifungal Resistance in Spain

Rivero-Menéndez, Olga; Soto-Debrán, Juan Carlos; Medina, Narda; Lúcio, José; Mellado, Emilia; Alastruey‐Izquierdo, Ana

doi:10.1128/aac.00865-19

Cited by 29 publications

(28 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We report the presence of TR 46 /Y121F/T289A now also from Iran, where until now only TR 34 /L98H had been isolated . This mutation, conferring voriconazole resistance, has been reported from both environmental (China, Taiwan, United Kingdom, Colombia, France, Germany, India, the Netherlands and Tanzania) and clinical sources (Spain, United Kingdom, France, Portugal, Argentina, Taiwan, Germany, China, Japan, United States, Denmark, Belgium and the Netherlands) (Table 1). All previous studies conducted in Iran for monitoring the mechanism of resistance among azole‐resistant A fumigatus in both clinical and environmental samples showed that the TR 34 /L98H mutation was reported with increasing frequency from 3.3% in 2013 to 6.6% in 2016 .…”

Section: Discussionmentioning

confidence: 73%

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran

Ahangarkani

Puts

Nabili

et al. 2020

Mycoses

View full text Add to dashboard Cite

Background: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management. Objective: Screening of environmental presence of azole-resistant A fumigatus in Iran.Methods: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar.Phenotypic MICs were obtained from selected, molecularly confirmed isolates.cyp51A gene sequencing and genotyping of azole-resistant isolates were done.Results: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR 46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype.Conclusion: This is the first report of A fumigatus with TR 46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region. K E Y W O R D SAspergillus fumigatus, azole resistance, compost, TR 34 /L98H, TR46/Y121F/T289A | 431 AHANGARKANI et Al.

show abstract

Section: Discussionmentioning

confidence: 73%

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran

Ahangarkani

Puts

Nabili

et al. 2020

Mycoses

View full text Add to dashboard Cite

show abstract

“…Annual surveys in five academic hospitals in the Netherlands showed that azole resistance in A. fumigatus has doubled from 2014 to 2018 [23,24]. Similar data have been reported worldwide [25][26][27][28][29][30][31][32][33][34][35], and an international resistance surveillance group has been set up by ISHAM/ECMM to capture more information on azole resistance worldwide [36,37].…”

Section: Diagnosis Of Aspergillosismentioning

confidence: 76%

“…The TR46/Y121F/T289A is a less widespread but emerging azole resistance mutation, which was first reported in the Netherlands in 2009 [60]. Both resistance mechanisms are regularly recovered from environmental isolates worldwide [31,[61][62][63][64][65][66][67][68][69][70][71], and therefore are likely to have developed resistance from the substantial use of environmental azole fungicides [31,55,69,[72][73][74][75][76][77][78]. In 2017, the first azole-resistant A. fumigatus cyp51A TR46/Y121F/T289A mutant was isolated in the UK from a patient that had no prior history of azole antifungal use, suggesting resistance must have been acquired through the environment [79].…”

Section: Azole Resistancementioning

confidence: 99%

Detecting Azole-Antifungal Resistance in Aspergillus fumigatus by Pyrosequencing

Torre

Frazer

Rautemaa‐Richardson

2020

JoF

View full text Add to dashboard Cite

Guidelines on the diagnosis and management of Aspergillus disease recommend a multi-test approach including CT scans, culture, fungal biomarker tests, microscopy and fungal PCR. The first-line treatment of confirmed invasive aspergillosis (IA) consists of drugs in the azole family; however, the emergence of azole-resistant isolates has negatively impacted the management of IA. Failure to detect azole-resistance dramatically increases the mortality rates of azole-treated patients. Despite drug susceptibility tests not being routinely performed currently, we suggest including resistance testing whilst diagnosing Aspergillus disease. Multiple tools, including DNA sequencing, are available to screen for drug-resistant Aspergillus in clinical samples. This is particularly beneficial as a large proportion of IA samples are culture negative, consequently impeding susceptibility testing through conventional methods. Pyrosequencing is a promising in-house DNA sequencing method that can rapidly screen for genetic hotspots associated with antifungal resistance. Pyrosequencing outperforms other susceptibility testing methods due to its fast turnaround time, accurate detection of polymorphisms within critical genes, including simultaneous detection of wild type and mutated sequences, and—most importantly—it is not limited to specific genes nor fungal species. Here we review current diagnostic methods and highlight the potential of pyrosequencing to aid in a diagnosis complete with a resistance profile to improve clinical outcomes.

show abstract

“…Several synonymous and non-synonymous point mutations were found among both susceptible and non-susceptible strains. One azole resistant strain (CM7668) harbored a c641t base change, resulting in a P214L point mutation that was only present in this strain, previously described in a recent work [ 36 ].…”

Section: Resultsmentioning

confidence: 98%

“… * A, azole drugs profile, S susceptible, R Resistant. 1 This mutation was previously described in a recent work [ 36 ]. …”

Section: Figurementioning

confidence: 99%

Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus

Lúcio

González-Jiménez

Rivero-Menéndez

et al. 2020

Genes

Self Cite

View full text Add to dashboard Cite

Infections caused by Aspergillus species are being increasingly reported. Aspergillus flavus is the second most common species within this genus causing invasive infections in humans, and isolates showing azole resistance have been recently described. A. flavus has three cyp51-related genes (cyp51A, cyp51B, and cyp51C) encoding 14-α sterol demethylase-like enzymes which are the target of azole drugs. In order to study triazole drug resistance in A. flavus, three strains showing reduced azole susceptibility and 17 azole susceptible isolates were compared. The three cyp51-related genes were amplified and sequenced. A comparison of the deduced Cyp51A, Cyp51B, and Cyp51C protein sequences with other protein sequences from orthologous genes in different filamentous fungi led to a protein identity that ranged from 50% to 80%. Cyp51A and Cyp51C presented several synonymous and non-synonymous point mutations among both susceptible and non-susceptible strains. However, two amino acid mutations were present only in two resistant isolates: one strain harbored a P214L substitution in Cyp51A, and another a H349R in Cyp51C that also showed an increase of cyp51A and cyp51C gene expression compared to the susceptible strain ATCC2004304. Isolates that showed reduced in vitro susceptibility to clinical azoles exhibited a different susceptibility profile to demethylation inhibitors (DMIs). Although P214L substitution might contribute to azole resistance, the role of H349R substitution together with changes in gene expression remains unclear.

show abstract

Molecular Identification, Antifungal Susceptibility Testing, and Mechanisms of Azole Resistance in Aspergillus Species Received within a Surveillance Program on Antifungal Resistance in Spain

Cited by 29 publications

References 50 publications

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran

Detecting Azole-Antifungal Resistance in Aspergillus fumigatus by Pyrosequencing

Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus

Contact Info

Product

Resources

About

Molecular Identification, Antifungal Susceptibility Testing, and Mechanisms of Azole Resistance in Aspergillus Species Received within a Surveillance Program on Antifungal Resistance in Spain

Cited by 29 publications

References 50 publications

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR46/Y121F/T289A mutation in Iran

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR46/Y121F/T289A mutation in Iran

Detecting Azole-Antifungal Resistance in Aspergillus fumigatus by Pyrosequencing

Point Mutations in the 14-α Sterol Demethylase Cyp51A or Cyp51C Could Contribute to Azole Resistance in Aspergillus flavus

Contact Info

Product

Resources

About

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran

First azole‐resistant Aspergillus fumigatus isolates with the environmental TR₄₆/Y121F/T289A mutation in Iran