Molecular epidemiology of Aspergillus fumigatus isolates harboring the TR34/L98H azole resistance mechanism.
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.
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Simone M T
SM
Camps
Antonius J M M
AJ
Rijs
Corné H W
CH
Klaassen
Jacques F
JF
Meis
Céline M
CM
O'Gorman
Paul S
PS
Dyer
Willem J G
WJ
Melchers
Paul E
PE
Verweij
D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000453:epidemiology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D001393:Azoles / Q000494:pharmacology*; D003433:Crosses, Genetic; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D025141:Drug Resistance, Fungal; D005060:Europe / Q000453:epidemiology; D005656:Fungal Proteins / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008826:Microbial Sensitivity Tests; D017720:Molecular Epidemiology; D009154:Mutation; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
D000935:Antifungal Agents; D001393:Azoles; D004271:DNA, Fungal; D005656:Fungal Proteins; D003577:Cytochrome P-450 Enzyme System; C465526:cytochrome P-450 CYP51A, Aspergillus