A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus
- PMID: 12604551
- PMCID: PMC149335
- DOI: 10.1128/AAC.47.3.1120-1124.2003
A point mutation in the 14alpha-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus
Erratum in
- Antimicrob Agents Chemother. 2004 Mar;48(3):1071
Abstract
The genes encoding 14alpha-sterol demethylases (cyp51A and cyp51B) were analyzed in 12 itraconazole (ITC)-resistant and three ITC-susceptible clinical isolates of Aspergillus fumigatus. Six ITC-resistant strains exhibited a substitution of another amino acid for glycine at position 54, which is located at a very conserved region of the Cyp51A protein. The cyp51A gene from the A. fumigatus wild-type strain (CM-237) was replaced with the mutated cyp51A gene copy of an ITC-resistant strain (AF-72). Two transformants exhibited resistance to ITC, both of which had incorporated the mutated copy of the cyp51A gene.
Similar articles
-
Substitutions at methionine 220 in the 14alpha-sterol demethylase (Cyp51A) of Aspergillus fumigatus are responsible for resistance in vitro to azole antifungal drugs.Antimicrob Agents Chemother. 2004 Jul;48(7):2747-50. doi: 10.1128/AAC.48.7.2747-2750.2004. Antimicrob Agents Chemother. 2004. PMID: 15215142 Free PMC article.
-
Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma.J Antimicrob Chemother. 2005 Jan;55(1):31-7. doi: 10.1093/jac/dkh507. Epub 2004 Nov 24. J Antimicrob Chemother. 2005. PMID: 15563516
-
Insight into the Significance of Aspergillus fumigatus cyp51A Polymorphisms.Antimicrob Agents Chemother. 2018 May 25;62(6):e00241-18. doi: 10.1128/AAC.00241-18. Print 2018 Jun. Antimicrob Agents Chemother. 2018. PMID: 29632011 Free PMC article.
-
Azole resistant Aspergillus fumigatus: an emerging problem.Med Mal Infect. 2013 Apr;43(4):139-45. doi: 10.1016/j.medmal.2013.02.010. Epub 2013 Apr 4. Med Mal Infect. 2013. PMID: 23562488 Review.
-
[The Current Status of Drug-resistant Aspergillus].Med Mycol J. 2016;57(3):J103-12. doi: 10.3314/mmj.16.001. Med Mycol J. 2016. PMID: 27581778 Review. Japanese.
Cited by
-
Resistance to voriconazole due to a G448S substitution in Aspergillus fumigatus in a patient with cerebral aspergillosis.J Clin Microbiol. 2012 Jul;50(7):2531-4. doi: 10.1128/JCM.00329-12. Epub 2012 May 9. J Clin Microbiol. 2012. PMID: 22573589 Free PMC article.
-
Selection Pressure Pathways and Mechanisms of Resistance to the Demethylation Inhibitor-Difenoconazole in Penicillium expansum.Front Microbiol. 2018 Oct 31;9:2472. doi: 10.3389/fmicb.2018.02472. eCollection 2018. Front Microbiol. 2018. PMID: 30429831 Free PMC article.
-
Genome-Wide Comparative Analysis of Aspergillus fumigatus Strains: The Reference Genome as a Matter of Concern.Genes (Basel). 2018 Jul 19;9(7):363. doi: 10.3390/genes9070363. Genes (Basel). 2018. PMID: 30029559 Free PMC article.
-
Heteroresistance to fluconazole in Cryptococcus neoformans is intrinsic and associated with virulence.Antimicrob Agents Chemother. 2009 Jul;53(7):2804-15. doi: 10.1128/AAC.00295-09. Epub 2009 May 4. Antimicrob Agents Chemother. 2009. PMID: 19414582 Free PMC article.
-
Aspergillus fumigatus strains with mutations in the cyp51A gene do not always show phenotypic resistance to itraconazole, voriconazole, or posaconazole.Antimicrob Agents Chemother. 2011 May;55(5):2460-2. doi: 10.1128/AAC.01358-10. Epub 2011 Feb 14. Antimicrob Agents Chemother. 2011. PMID: 21321141 Free PMC article.
References
-
- Chryssanthou, E. 1997. In vitro susceptibility of respiratory isolates of Aspergillus species to itraconazole and amphotericin B. acquired resistance to itraconazole. Scand. J. Infect. Dis. 29:509-512. - PubMed
-
- Cove, D. J. 1966. The induction and repression of nitrate reductase in the fungus Aspergillus nidulans. Biochim. Biophys. Acta 113:51-56. - PubMed
-
- Cuenca-Estrella, M., J. L. Rodriguez-Tudela, E. Mellado, J. V. Martinez-Suarez, and A. Monzon. 1998. Comparison of the in vitro activity of voriconazole (UK-109,496), itraconazole and amphotericin B against clinical isolates of Aspergillus fumigatus. J. Antimicrob. Chemother. 42:531-533. - PubMed
-
- Dannaoui, E., E. Borel, M. F. Monier, M. A. Piens, S. Picot, and F. Persat. 2001. Acquired itraconazole resistance in Aspergillus fumigatus. J. Antimicrob. Chemother. 47:333-340. - PubMed
-
- Dannaoui, E., E. Borel, F. Persat, M. F. Monier, M. A. Piens, the EGBA Network, and the European Research Group on Biotypes and Genotypes of Aspergillus fumigatus. 1999. In-vivo itraconazole resistance of Aspergillus fumigatus in systemic murine aspergillosis. J. Med. Microbiol. 48:1087-1093. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources