Genetic relatedness of multi-azole resistant Aspergillus fumigatus isolates

S.M.T. Camps, P.E. Verweij, W.J.G. Melchers

Author address: 

Department of Medical microbiology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands


Objectives In the last few years multi-azole resistant Aspergillus fumigatus seem to emerge in the Netherlands. The dominant resistance mechanism is a point mutation in the cyp51A gene resulting in the substitution of leucine to histidine at codon 98 (L98H) combined with a 34 bp tandem repeat (TR) in the promoter region of this gene. The emergence of this single resistance mechanism suggests that the resistant isolates have a common evolutionary origin. We analyzed the CSP gene, microsatellites and the mating type locus to study azole susceptible and resistant A. fumigatus isolates of clinical and environmental origin to investigate the genetic relatedness of TR/L98H isolates. Methods Resistant isolates containing the TR/L98H resistance mechanism (n=57) were subjected to CSP, microsatellite and mating type analysis. As a control, both susceptible (n=57) and resistant isolates without the TR/L98H resistance mechanism (n=17) were analyzed. Results The TR/L98H isolates clustered together in microsatellite analysis and were grouped into three CSP types (2, 4B and 11). Susceptible and non-TR/L98H resistant control isolates were classified to other CSP types than the TR/L98H isolates, except for several isolates belonging to CSP type 2. Mating type genes MAT1-1 and MAT1-2 were almost equally represented in each group. Conclusions 1. Clinical and environmental TR/L98H isolates were grouped to the same CSP types and clustered together using microsatellite typing, indicating that the TR/L98H resistance mechanism has only recently developed and might not be induced in the patient but might be acquired from the environment. 2. As the TR/L98H isolates grouped to different CSP types and clustered apart from the control isolates, the TR/L98H isolates might belong to a separate genetic A. fumigatus lineage. 3. Although microsatellite and CSP analysis indicate that the TR/L98H isolates are rather homogeneous, segregation of the mating type locus is equal to the control isolates. This might suggest that sexual reproduction played a role in resistance development.

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Full conference title: 

    • ECFG 10th (2010)