Mutations in the Cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus isolated from avian farms in France and China

Wang, Dong Ying; Gricourt, Marine; Arné, Pascal; Thierry, Simon; Seguin, Dominique; Chermette, René; Huang, Wei Yi; Dannaoui, Éric; Botterel, Françoise; Guillot, Jacques

doi:10.3382/ps.2013-03541

Cited by 20 publications

(12 citation statements)

References 16 publications

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“…The first strain with these mutations to be described was isolated in 2001 from a clinical sample in a Spanish hospital (5). These strains have now been reported in many European countries (6-10, 13, 20, 21), the United States (22), Canada (23), India (15), China (24), and Australia (16). Some authors have reported that these substitutions are not associated with azole resistance (5,25).…”

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confidence: 99%

Insight into the Significance of Aspergillus fumigatus cyp51A Polymorphisms

Garcia-Rubio

Alcàzar-Fuoli

Monteiro

et al. 2018

Antimicrob Agents Chemother

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Triazole antifungal compounds are the first treatment choice for invasive aspergillosis. However, in the last decade the rate of azole resistance among strains has increased notoriously. The main resistance mechanisms are well defined and mostly related to point mutations of the azole target, 14-α sterol demethylase (), with or without tandem repeat integrations in the promoter. Furthermore, different combinations of five Cyp51A mutations (F46Y, M172V, N248T, D255E, and E427K) have been reported worldwide in about 10% of all isolates tested. The azole susceptibility profile of these strains shows elevated azole MICs, although on the basis of the azole susceptibility breakpoints, these strains are not considered azole resistant. The purpose of the study was to determine whether these polymorphisms (single nucleotide polymorphisms [SNPs]) are responsible for the azole susceptibility profile and whether they are reflected in a poorer azole treatment response that could compromise patient treatment and outcome. A mutant with a deletion was generated and became fully susceptible to all azoles tested. Also, three gene constructions with different combinations of SNPs were generated and reintroduced into an azole-susceptible wild-type (WT) strain (the Δ strain). The alternative model host was used to compare the virulence and voriconazole response of larvae infected with strains with WT or with SNPs. All strains were pathogenic in larvae, although they did not respond similarly to voriconazole therapeutic doses. Finally, the full genomes of these strains were sequenced and analyzed in comparison with those of WT strains, revealing that they belong to different strain clusters or lineages.

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confidence: 99%

Insight into the Significance of Aspergillus fumigatus cyp51A Polymorphisms

Garcia-Rubio

Alcàzar-Fuoli

Monteiro

et al. 2018

Antimicrob Agents Chemother

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“…All three cities are located in the east or southeast of China. AT present, the epidemiology of azole resistance in A. fumigatus in different parts of China and its association with azole fungicides in agriculture are still largely unknown since susceptibility testing is not routinely performed in clinical microbiology laboratories and azole-resistant strains have not yet been identified from environmental sources (14). In the present study, we sought to investigate the occurrence and characteristics of azole resistance in clinical and environmental A. fumigatus isolates from different geographic areas in China and explore the genetic relatedness of azole-resistant isolates from China and international collections through putative cell surface protein (CSP) and microsatellite genotyping.…”

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confidence: 99%

Epidemiology and Molecular Characterizations of Azole Resistance in Clinical and Environmental Aspergillus fumigatus Isolates from China

Chen

Zhao

et al. 2016

Antimicrob Agents Chemother

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i Azole resistance in Aspergillus fumigatus has emerged as a worldwide public health problem. We sought here to demonstrate the occurrence and characteristics of azole resistance in A. fumigatus from different parts of China. A total of 317 clinical and 144 environmental A. fumigatus isolates from 12 provinces were collected and subjected to screening for azole resistance. Antifungal susceptibility, cyp51A gene sequencing, and genotyping were carried out for all suspected azole-resistant isolates and a subset of azole-susceptible isolates. As a result, 8 (2.5%) clinical and 2 (1.4%) environmental A. fumigatus isolates were identified as azole resistant. Five azole-resistant strains exhibit the TR 34 /L98H mutation, whereas four carry the TR 34 /L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR 34 / L98H isolates, while the TR 34 /L98H/S297T/F495I isolates from China harbored a distinct genetic background with resistant isolates from other countries. High polymorphisms existed in the cyp51A gene that produced amino acid changes among azolesusceptible A. fumigatus isolates, with N248K being the most common mutation. These data suggest that the wide distribution of azole-resistant A. fumigatus might be attributed to the environmental resistance mechanisms in China.

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“…Regarding poultry farms, the use of azoles for prophylaxis and treatment of aspergillosis is unusual, owing to concerns regarding the existence of drug residues in meat and the expense. However, unusual circumstances could lead to antifungal prophylaxis on farms [82]. On the other hand, the use of azoles for decontaminating bedding and environmental disinfection is common [51,70,71,[82][83][84][85].…”

Section: Aspergillosis In Avian Speciesmentioning

confidence: 99%

“…Regarding avian species, despite the importance of aspergillosis in these animals, there are few studies evaluating resistance or cryptic species. The majority of those reports are in poultry, and the rate of resistance is considered low thus far [70,82,108,109]. On the other hand, a few reports on Aspergillus susceptibility studies isolated from captive wild birds are described [110,111].…”

Section: Aspergillus Azole Resistancementioning

confidence: 99%

Aspergillosis, Avian Species and the One Health Perspective: The Possible Importance of Birds in Azole Resistance

et al. 2020

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The One Health context considers health based on three pillars: humans, animals, and environment. This approach is a strong ally in the surveillance of infectious diseases and in the development of prevention strategies. Aspergillus spp. are fungi that fit substantially in this context, in view of their ubiquity, as well as their importance as plant pathogens, and potentially fatal pathogens for, particularly, humans and avian species. In addition, the emergence of azole resistance, mainly in Aspergillus fumigatus sensu stricto, and the proven role of fungicides widely used on crops, reinforces the need for a multidisciplinary approach to this problem. Avian species are involved in short and long distance travel between different types of landscapes, such as agricultural fields, natural environments and urban environments. Thus, birds can play an important role in the dispersion of Aspergillus, and of special concern, azole-resistant strains. In addition, some bird species are particularly susceptible to aspergillosis. Therefore, avian aspergillosis could be considered as an environmental health indicator. In this review, aspergillosis in humans and birds will be discussed, with focus on the presence of Aspergillus in the environment. We will relate these issues with the emergence of azole resistance on Aspergillus. These topics will be therefore considered and reviewed from the “One Health” perspective.

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Mutations in the Cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus isolated from avian farms in France and China

Cited by 20 publications

References 16 publications

Insight into the Significance of Aspergillus fumigatus cyp51A Polymorphisms

Insight into the Significance of Aspergillus fumigatus cyp51A Polymorphisms

Epidemiology and Molecular Characterizations of Azole Resistance in Clinical and Environmental Aspergillus fumigatus Isolates from China

Aspergillosis, Avian Species and the One Health Perspective: The Possible Importance of Birds in Azole Resistance

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