scholarly journals Molecular Epidemiology of Azole-Resistant Aspergillus fumigatus in Sawmills of Eastern France by Microsatellite Genotyping

2020 ◽  
Vol 6 (3) ◽  
pp. 120
Author(s):  
Audrey Jeanvoine ◽  
Chloé Godeau ◽  
Audrey Laboissière ◽  
Gabriel Reboux ◽  
Laurence Millon ◽  
...  

Background: Wood chipping has been described as a potential hotspot for the selection of azole-resistant Aspergillus fumigatus (ARAf). We previously reported ARAf isolates in sawmills (Eastern France), most of which contained the TR34/L98H mutation. Methods: To study genotypic relatedness, microsatellite genotyping (short tandem repeat for A. fumigatus (STRAf)) was performed on 41 azole-susceptible A. fumigatus (ASAf) and 23 ARAf isolated from 18 sawmills and two clinical A. fumigatus (sensitive and resistant) isolated from a sinus sample of a woodworker. Results: Fifty-four unique multilocus genotypes (MLGs) were described among the 66 isolates: 13/24 ARAf and 41/42 ASAf. Allelic diversity was higher for ASAf than for ARAf. Among the 24 ARAf, five isolates had their own MLGs. Thirteen ARAf (54%) belonged to the same group, composed of four close MLGs, defined using Bruvo’s distance. Thirty-two of the 42 ASAf (76%) had their own MLGs and could not be grouped with the Bruvo’s distance cutoff used (0.2). Conclusion: Thus, at a regional scale and in the particular environment of the wood industry, common but also different distinct genotypes, even in the same sawmill, were identified. This suggests that the hypothesis of ARAf clonal expansion from a common strain is probably insufficient to explain genotype emergence and distribution.

2019 ◽  
Vol 21 (3) ◽  
pp. 483-490 ◽  
Author(s):  
Jennifer Tyler ◽  
Lorie Kumer ◽  
Carolyn Fisher ◽  
Heather Casey ◽  
Hiroko Shike

2020 ◽  
Vol 6 (4) ◽  
pp. 277
Author(s):  
Jianhua Zhang ◽  
Jan Zoll ◽  
Tobias Engel ◽  
Joost van den Heuvel ◽  
Paul E. Verweij ◽  
...  

Azole-resistant Aspergillus fumigatus isolates recovered at high frequency from patients, harbor mutations that are associated with variation of promoter length in the cyp51A gene. Following the discovery of the TR34/L98H genotype, new variations in tandem repeat (TR) length and number of repeats were identified, as well as additional single nucleotide polymorphisms (SNPs) in the cyp51A gene, indicating that the diversity of resistance mutations in A. fumigatus is likely to continue to increase. Investigating the development routes of TR variants is critical to be able to design preventive interventions. In this study, we tested the potential effects of azole exposure on the selection of TR variations, while allowing haploid A. fumigatus to undergo asexual reproduction. Through experimental evolution involving voriconazole (VOR) exposure, an isolate harboring TR343/L98H evolved from a clinical TR34/L98H ancestor isolate, confirmed by whole genome sequencing. TR343/L98H was associated with increased cyp51A expression and high VOR and posaconazole MICs, although additional acquired SNPs could also have contributed to the highly azole-resistant phenotype. Exposure to medical azoles was found to select for TR343, thus supporting the possibility of in-host selection of TR34 variants.


2011 ◽  
Vol 56 (1) ◽  
pp. 174-178 ◽  
Author(s):  
Pilar Escribano ◽  
Sandra Recio ◽  
Teresa Peláez ◽  
Milagros González-Rivera ◽  
Emilio Bouza ◽  
...  

ABSTRACTSecondary resistance to azoles inAspergillus fumigatusisolates from patients taking long-term itraconazole therapy has been described. We studied the acquisition of secondary azole resistance in 20A. fumigatusisolates with no mutations at codon 54, 98, 138, 220, 432, or 448 in thecyp51Agene. Adjusted conidium inocula (3 × 107CFU/ml) of each isolate were prepared and progressively or directly exposed to increasing itraconazole concentrations, ranging from 0.5 μg/ml to 16 μg/ml. Itraconazole, voriconazole, and posaconazole MICs were determined using the CLSI M38-A2 procedure before (MICinitial) and after (MICfinal) exposure to itraconazole. In both procedures, the MICfinalwas significantly higher than the MICinitial. However, after progressive exposure to itraconazole, the MICs of the three azoles were higher than after direct exposure. No mutations were found at codon 54, 98, 138, 220, 432, or 448 in thecyp51Agene of isolates growing at the highest concentration of itraconazole. More concentrated conidium inocula (2 × 109CFU/ml) plated in itraconazole at 4 μg/ml revealed the presence of heteroresistant populations in two initially wild-type isolates. These isolates became resistant to itraconazole and posaconazole only after use of the concentrated inoculum. These heteroresistant isolates harbored a mutation at codon G54, and the MICs of itraconazole and posaconazole were >16 μg/ml. In all procedures,A. fumigatusshort tandem repeat (STRAf) typing was used to demonstrate that the genotype did not change before or after exposure to itraconazole.


2013 ◽  
Vol 7 (3) ◽  
pp. e78-e79 ◽  
Author(s):  
Hong-dan Wang ◽  
Shi-xiu Liao ◽  
Chun-mei Shen ◽  
Wen-juan Liu ◽  
Guo-lian Yuan ◽  
...  

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