2014
DOI: 10.1093/jac/dku316
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Aspergillus fumigatus harbouring the sole Y121F mutation shows decreased susceptibility to voriconazole but maintained susceptibility to itraconazole and posaconazole

Abstract: Taken together, these observations suggest an original mechanism conferring resistance to azoles mediated by cyp51A of environmental origin. This uncommon susceptibility pattern might represent a 'missing link' between the wild-type A. fumigatus and the fully azole-resistant strain harbouring the TR46/Y121F/T289A mutations.

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Cited by 45 publications
(32 citation statements)
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“…In A. fumigatus, many cases of azole resistance have been linked to cyp51A single point mutations that lead to amino acid alterations in the Cyp51A protein, as well as tandem repeats in the promoter region of the cyp51A gene that enhance its expression (37)(38)(39)(40)(41). Interestingly, no amino acid substitutions in the Cyp51B protein have been correlated to azole resistance so far, which is also indicative of its smaller role in azole response.…”
Section: Discussionmentioning
confidence: 99%
“…In A. fumigatus, many cases of azole resistance have been linked to cyp51A single point mutations that lead to amino acid alterations in the Cyp51A protein, as well as tandem repeats in the promoter region of the cyp51A gene that enhance its expression (37)(38)(39)(40)(41). Interestingly, no amino acid substitutions in the Cyp51B protein have been correlated to azole resistance so far, which is also indicative of its smaller role in azole response.…”
Section: Discussionmentioning
confidence: 99%
“…However, one of the resistance mechanisms consisting of a 34 base pair (bp) sequence tandem repeat (TR34) in the promoter region of the cyp51A gene in combination with an L98H substitution has been reported to be predominant in azole‐resistant A. fumigatus isolates from environmental sources, treatment‐naive subjects, and patients under treatment, molecular investigations suggested that use of azole fungicides in the environment selects multiple‐triazole‐resistant A. fumigatus TR 34 /L98H strains. This issue is further complicated by the emergence of a new resistance mechanism, TR46/Y121F/T289A in the cyp51A gene responsible for voriconazole resistance in A. fumigatus , which was detected with a single Y121F substitution without the TR46 or T289A alterations . Moreover, RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression, typically by causing the destruction of mRNA molecules in a sequence‐specific manner.…”
Section: Introductionmentioning
confidence: 99%
“…Numerous single point mutations in A. fumigatus cyp51A lead to resistance, where the most common include amino acid substitutions of glycine at codon 54 (G54), proline at codon 216 (P216), phenylalanine at codon 219 (F219), methionine at codon 220 (M220), and glycine at codon 448 (G448) ( Table 1) ( [18,26,54,[80][81][82][83][84][85][86][87][88][89][90][91][92][93] and reviewed in [94]). Other resistance mechanisms are described to be a combination of point mutations or the less common TR53 [89,[95][96][97][98][99][100][101][102].…”
Section: Azole Resistancementioning
confidence: 99%