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. 2012 Aug;50(8):2674-80.
doi: 10.1128/JCM.00335-12. Epub 2012 Jun 6.

Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism

Simone M T Camps  1 , Antonius J M M Rijs, Corné H W Klaassen, Jacques F Meis, Céline M O'Gorman, Paul S Dyer, Willem J G Melchers, Paul E Verweij
Affiliations

Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism

Simone M T Camps et al. J Clin Microbiol. 2012 Aug.

Abstract

A rapid emergence of azole resistance has been observed in Aspergillus fumigatus in The Netherlands over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves the TR(34)/L98H mutations in cyp51A. This resistance mechanism is now also increasingly being found in other countries. Therefore, genetic markers were used to gain more insights into the origin and spread of this genotype. Studies of 142 European isolates revealed that those with the TR(34)/L98H resistance mechanism showed less genetic variation than azole-susceptible isolates or those with a different genetic basis of resistance and were assigned to only four CSP (putative cell surface protein) types. Sexual crossing experiments demonstrated that TR(34)/L98H isolates could outcross with azole-susceptible isolates of different genetic backgrounds, suggesting that TR(34)/L98H isolates can undergo the sexual cycle in nature. Overall, our findings suggest a common ancestor of the TR(34)/L98H mechanism and subsequent migration of isolates harboring TR(34)/L98H across Europe.

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Figures

Fig 1
Fig 1
Distribution of CSP types of 55 TR34/L98H A. fumigatus isolates isolated between 1998 and 2007 in The Netherlands.
Fig 2
Fig 2
Minimum spanning tree showing the genotypic relationship between the azole-resistant and azole-susceptible A. fumigatus isolates. Each circle corresponds to a unique genotype, and the size of the circle corresponds to the number of isolates with that genotype (1, 2, or 3 isolates). Connecting lines correspond to the number of different microsatellite loci between the genotypes. Short bold line, 1 difference; black line, 2 differences; long gray line, 3 differences; dotted line, 4 or more differences. Red, azole-resistant TR34/L98H, The Netherlands (n = 55); yellow, azole-susceptible wild type, The Netherlands (n = 55); blue, azole-resistant non-TR34/L98H, The Netherlands (n = 7); pink, azole-resistant TR34/L98H, other European countries (n = 25).
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