Interrogation of related clinical pan-azole-resistant Aspergillus fumigatus strains: G138C, Y431C, and G434C single nucleotide polymorphisms in cyp51A, upregulation of cyp51A, and integration and activation of transposon Atf1 in the cyp51A promoter

Antimicrobial Agents and Chemotherapy

Volumn 55, Issue 11, 2011, Pages 5113-5121

  Albarrag, Ahmed M ^a,b   Anderson, Michael J ^b   Howard, Susan J ^b   Robson, Geoff D ^b   Warn, Peter A ^b,c   Sanglard, Dominique ^d   Denning, David W ^a,b,c,d  

^a KING SAUD UNIVERSITY   (Saudi Arabia)

^b UNIVERSITY OF MANCHESTER   (United Kingdom)

^c MANCHESTER UNIVERSITY NHS FOUNDATION TRUST   (United Kingdom)

^d LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIFUNGAL AGENT; ITRACONAZOLE; MESSENGER RNA; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 4; PAN AZOLE; UNCLASSIFIED DRUG;

ARTICLE; ASPERGILLUS FUMIGATUS; ATF1 GENE; CONTROLLED STUDY; CYP51A GENE; FUNGAL GENE; FUNGAL STRAIN; FUNGUS GROWTH; FUNGUS ISOLATION; GENE DUPLICATION; GENE EXPRESSION; GENE IDENTIFICATION; GENE INSERTION; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRIORITY JOURNAL; SACCHAROMYCES CEREVISIAE; SINGLE NUCLEOTIDE POLYMORPHISM; TRANSPOSON; UPREGULATION;

ANTIFUNGAL AGENTS; ASPERGILLUS FUMIGATUS; AZOLES; CYTOCHROME P-450 ENZYME SYSTEM; DNA TRANSPOSABLE ELEMENTS; DRUG RESISTANCE, FUNGAL; FUNGAL PROTEINS; POLYMORPHISM, SINGLE NUCLEOTIDE; PROMOTER REGIONS, GENETIC;

EID: 80054697382     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00517-11     Document Type: Article

References (44)

1. Anderson, M. J., K. Gull, and D. W. Denning. 1996. Molecular typing by random amplification of polymorphic DNA and M13 Southern hybridization of related paired isolates of Aspergillus fumigatus. J. Clin. Microbiol. 34:87-93. (Pubitemid 126506900)
2. Araujo, R., and A. Rodrigues. 2004. Variability of germinative potential among pathogenic species of Aspergillus. J. Clin. Microbiol. 42:4335-4337. (Pubitemid 39296172)
3. Balajee, S. A., J. L. Gribskov, H. Edward, D. Nickle, and K. A. Marr. 2005. Aspergillus lentulus sp. nov., a new sibling species of A. fumigates. Eukaryot. Cell 4:625-632. (Pubitemid 40383765)
4. Bart-Delabesse, E., J. F. Humbert, E. Delabesse, and S. Bretagne. 1998. Microsatellite markers for typing Aspergillus fumigatus isolates. J. Clin. Microbiol. 36:2413-2418. (Pubitemid 28380928)
5. Bueid, A., et al. 2010. Azole antifungal resistance in Aspergillus fumigatus: 2008 and 2009. J. Antimicrob. Chemother. 65:2116-2118.
6. Chen, J., H. Li, R. Li, D. Bu, and Z. Wan. 2005. Mutations in the cyp51A gene and susceptibility to itraconazole in Aspergillus fumigatus serially isolated from a patient with lung aspergilloma. J. Antimicrob. Chemother. 55:31-37. (Pubitemid 40192611)
7. Da Silva Ferreira, M. E., et al. 2004. In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves multiple mechanisms of resistance. Antimicrob. Agents Chemother. 48:4405-4413. (Pubitemid 39434904)
8. Denning, D. W., A. Pleuvry, and D. C. Cole. 2010. Global burden of allergic bronchopulmonary aspergillosis (ABPA) complicating asthma. Thorax 65(Suppl. 4):A155-A155.
9. Denning, D. W., A. Pleuvry, and D. C. Cole. 2010. Global burden of chronic pulmonary aspergillosis as a sequel to pulmonary tuberculosis. Bull. WHO, in press.
10. Denning, D. W., et al. 1997. Itraconazole resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. 41:1364-1368. (Pubitemid 27231443)
11. Diaz-Guerra, T. M., E. Mellado, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2003. A point mutation in the 14α-sterol demethylase gene cyp51A contributes to itraconazole resistance in Aspergillus fumigatus. Antimicrob. Agents Chemother. 47:1120-1124.
12. Fedorova, N., et al. 2008. Genomic islands in the pathogenic filamentous fungus Aspergillus fumigatus. PLoS Genet. 4:e1000046.
13. Heilmann, C. J., S. Schneider, K. S. Barker, P. D. Rogers, and J. Morschhäuser. 2010. An A643T mutation in the transcription factor Upc2p causes constitutive ERG11 upregulation and increased fluconazole resistance in Candida albicans. Antimicrob. Agents Chemother. 54:353-359.
14. Hey, P., G. Robson, M. Birch, and M. Bromley. 2008. Characterisation of Aft1 a Fot1/Pogo type transposon of Aspergillus fumigatus. Fungal Genet. Biol. 45:117-126.
15. Howard, S. J., and M. C. Arendrup. 2011. Acquired antifungal drug resistance in Aspergillus fumigatus: epidemiology and detection. Med. Mycol. 49(Suppl. 1):S90-S95.
16. Howard, S. J., et al. 2009. Frequency and evolution of azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg. Infect. Dis. 15:1068-1076.
17. Howard, S. J., et al. 2006. Multi-azole resistance in Aspergillus fumigatus. Int. J. Antimicrob. Agents. 28:450-453. (Pubitemid 44740492)
18. Kelly, S. L., D. C. Lamb, A. J. Corran, B. C. Baldwin, and D. E. Kelly. 1995. Mode of action and resistance to azole antifungals associated with the formation of 14 alpha-methylergosta-8,24(28)-dien-3 beta,6 alpha-diol. Biochem. Biophys. Res. Commun. 207:910-915.
19. Lehrnbecher, T., et al. 2010. Trends in the postmortem epidemiology of invasive fungal infections at a university hospital. J. Infect. 61:259-265.
20. Manavathu, E. K., I. Baskaran, S. Krishnan, G. Alangaden, and P. H. Chandrasekar. 2003. Abstr. 43rd Intersci. Conf. Antimicrob. Agents Chemother., abstr. M-471.
21. Manavathu, E. K., J. A. Vazquez, and P. H. Chandrasekar. 1999. Reduced susceptibility in laboratory-selected mutants of Aspergillus fumigatus to itraconazole due to decreased intracellular accumulation of the antifungal agent. Int. J. Antimicrob. Agents. 12:213-219. (Pubitemid 29335932)
22. Mann, P. A., et al. 2003. Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome P450 14α-demethylase. Antimicrob. Agents Chemother. 47:577-581. (Pubitemid 36158085)
23. Mellado, E., T. M. Diaz-Guerra, M. Cuenca-Estrella, and J. L. Rodriguez-Tudela. 2001. Identification of two different 14-α sterol demethylase-related genes (cyp51A and cyp51B) in Aspergillus fumigatus and other Aspergillus species. J. Clin. Microbiol. 39:2431-2438. (Pubitemid 32606215)
24. Mellado, E., et al. 2007. A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob. Agents Chemother. 51:1897-1904. (Pubitemid 46903071)
25. Mellado, E., et al. 2005. Targeted gene disruption of the 14-α sterol demethylase (cyp51A) in Aspergillus fumigatus and its role in azole drug susceptibility. Antimicrob. Agents Chemother. 49:2536-2538. (Pubitemid 40734499)
26. Nam, H. S., et al. 2010. Clinical characteristics and treatment outcomes of chronic necrotizing pulmonary aspergillosis: a review of 43 cases. Int. J. Infect. Dis. 14:e479-482.
27. Nascimento, A. M., et al. 2003. Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob. Agents Chemother. 47:1719-1726. (Pubitemid 36548560)
28. Nierman, W., et al. 2005. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438:1151-1156. (Pubitemid 41831684)
29. Osherov, N., D. P. Kontoyiannis, A. Romans, and G. S. May. 2001. Resistance to itraconazole in Aspergillus nidulans and Aspergillus fumigatus is conferred by extra copies of the A. nidulans P-450 14alpha-demethylase gene, pdmA. J. Antimicrob. Chemother. 48:75-81. (Pubitemid 32684728)
30. Paisley, D., G. D. Robson, and D. W. Denning. 2005. Correlation between in vitro growth rate and in vivo virulence in Aspergillus fumigatus. Med. Mycol. 43:397-401. (Pubitemid 41283042)
31. Pfaffl, M. W., G. W. Horgan, and L. Dempfle. 2002. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res. 30:e36.
32. Pfaller, M. A., et al. 2009. Wild-type MIC distribution and epidemiological cutoff values for Aspergillus fumigatus and three triazoles as determined by the Clinical and Laboratory Standards Institute broth microdilution methods. J. Clin. Microbiol. 47:3142-3146.
33. Pringle, A., et al. 2005. Cryptic speciation in the cosmopolitan and clonal human pathogenic fungus Aspergillus fumigatus. Evolution 59:1886-1899. (Pubitemid 41384373)
34. Rodriguez-Tudela, J. L., et al. 2008. Epidemiological cutoffs and cross-resistance to azole drugs in Aspergillus fumigatus. Antimicrob. Agents Chemother. 52:2468-2472. (Pubitemid 351915677)
35. Robson, G. D., M. G. Wiebe, B. Cunliffe, and A. P. Trinci. 1995. Choline- and acetylcholine-induced changes in the morphology of Fusarium graminearum: evidence for the involvement of the choline transport system and acetylcholinesterase. Microbiology 141:1309-1314.
36. Slaven, J. W., et al. 2002. Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genet. Biol. 36:199-206.
37. Snelders, E., et al. 2008. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med. 5:e219.
38. Steele, G. C., and A. P. Trinci. 1975. Morphology and growth kinetics of hyphae of differentiated and undifferentiated mycelia of Neurospora crassa. J. Gen. Microbiol. 91:362-368.
39. Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee on Antimicrobial Susceptibility Testing EUCAST. 2008. EUCAST technical note on method for the determination of broth dilution minimum inhibitory concentrations of antifungal agents for conidia-forming moulds. Clin. Microbiol. Infect. 14:982-984.
40. Tobin, M. B., R. B. Peery, and P. L. Skatrud. 1997. An electrophoretic molecular karyotype of a clinical isolate of Aspergillus fumigatus and localization of the MDR-like genes AfuMDR1 and AfuMDR2. Diagn. Microbiol. Infect. Dis. 29:67-71. (Pubitemid 27502208)
41. Trinci, A. P. 1974. A study of the kinetics of hyphal extension and branch initiation of fungal mycelia. J. Gen. Microbiol. 81:225-236.
42. Verweij, P. E., S. J. Howard, W. J. G. Melchers, and D. W. Denning. 2009. Azole-resistance in Aspergillus: proposed nomenclature and breakpoints. Drug Resist. Updat. 12:141-147.
43. Vogel, H. J. 1956. A convenient growth medium for Neurospora (medium N). Microbiol. Genet. Bull. 13:42-44.
44. Walsh, T. J., et al. 2008. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin. Infect. Dis. 46:327-360. (Pubitemid 351265310)