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PMID: 14576140 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

G484S amino acid substitution in lanosterol 14-alpha demethylase (ERG11) is related to fluconazole resistance in a recurrent Cryptococcus neoformans clinical isolate.

Antimicrobial agents and chemotherapy ·Vol. 47 ·No. 11 ·2003-11-00 ·Pages 3653-6

Rodero L, Mellado E, Rodriguez AC, Salve A, Guelfand L, Cahn P, Cuenca-Estrella M, Davel G, Rodriguez-Tudela JL

Abstract

Five sequential Cryptococcus neoformans isolates recovered from an AIDS patient with recurrent meningitis were analyzed. Four isolates were fluconazole susceptible, while the fifth isolate developed fluconazole resistance. Analysis of the 14-alpha lanosterol demethylase gene (ERG11) showed a point mutation in the resistant strain responsible for the amino acid substitution G484S.

MeSH Terms
Acquired Immunodeficiency Syndrome/complications Adult Amino Acid Sequence Amino Acid Substitution Antifungal Agents/pharmacology Cloning, Molecular Cryptococcus neoformans/drug effects Cytochrome P-450 Enzyme System/genetics Drug Resistance, Fungal/genetics Fluconazole/pharmacology Genotype Humans Male Meningitis, Cryptococcal/microbiology Microbial Sensitivity Tests Molecular Sequence Data Oxidoreductases/genetics Plasmids Point Mutation/genetics Recurrence Sterol 14-Demethylase
Chemicals
Antifungal Agents CYP51A1 protein, human Fluconazole Cytochrome P-450 Enzyme System Oxidoreductases Sterol 14-Demethylase
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Rodero Laura
Departamento Micología, Instituto Nacional de Enfermedades Infecciosas, ANLIS Dr. Carlos G. Malbrán, Hospital J. A. Fernandez, Buenos Aires, Argentina. [email protected]
Mellado Emilia
Rodriguez A Carolina
Salve Angela
Guelfand Liliana
Cahn Pedro
Cuenca-Estrella Manuel
Davel Graciela
Rodriguez-Tudela Juan L
References (13)
13 references, click to expand
  1. Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole.
    Mol Microbiol. 2003 Jan;47(2):357-71 PMID: 12519188
  2. Fluconazole tolerance in clinical isolates of Cryptococcus neoformans.
    Antimicrob Agents Chemother. 1997 Apr;41(4):748-51 PMID: 9087482
  3. Involvement of multiple Cryptococcus neoformans strains in a single episode of cryptococcosis and reinfection with novel strains in recurrent infection demonstrated by random amplification of polymorphic DNA and DNA fingerprinting.
    J Clin Microbiol. 1995 Jun;33(6):1682-3 PMID: 7650217
  4. Drug resistance in Cryptococcus neoformans.
    Drug Resist Updat. 1999 Aug;2(4):259-269 PMID: 11504497
  5. Development of azole resistance during fluconazole maintenance therapy for AIDS-associated cryptococcal disease.
    AIDS. 2001 Nov 23;15(17):2344-5 PMID: 11698718
  6. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer.
    Gene. 1988 Dec 15;73(1):237-44 PMID: 3243435
  7. Heterogeneous mechanisms of azole resistance in Candida albicans clinical isolates from an HIV-infected patient on continuous fluconazole therapy for oropharyngeal candidosis.
    J Antimicrob Chemother. 2002 Mar;49(3):515-24 PMID: 11864952
  8. Amino acid substitutions in the cytochrome P-450 lanosterol 14alpha-demethylase (CYP51A1) from azole-resistant Candida albicans clinical isolates contribute to resistance to azole antifungal agents.
    Antimicrob Agents Chemother. 1998 Feb;42(2):241-53 PMID: 9527767
  9. The G464S amino acid substitution in Candida albicans sterol 14alpha-demethylase causes fluconazole resistance in the clinic through reduced affinity.
    Biochem Biophys Res Commun. 1999 Aug 19;262(1):174-9 PMID: 10448088
  10. Persistence of initial infection in recurrent Cryptococcus neoformans meningitis.
    Lancet. 1993 Mar 6;341(8845):595-6 PMID: 8094831
  11. Multiple resistant phenotypes of Candida albicans coexist during episodes of oropharyngeal candidiasis in human immunodeficiency virus-infected patients.
    Antimicrob Agents Chemother. 1999 Jul;43(7):1621-30 PMID: 10390213
  12. Influence of shaking on antifungal susceptibility testing of Cryptococcus neoformans: a comparison of the NCCLS standard M27A medium, buffered yeast nitrogen base, and RPMI-2% glucose.
    Antimicrob Agents Chemother. 2000 Feb;44(2):400-4 PMID: 10639369
  13. Increased fluconazole resistance of Cryptococcus neoformans isolated from a patient with AIDS and recurrent meningitis.
    Clin Infect Dis. 1994 Nov;19(5):975-6 PMID: 7893896
Article Info
Journal
Antimicrobial agents and chemotherapy
Abbr.
Antimicrob Agents Chemother
ISSN
0066-4804
DOI
10.1128/AAC.47.11.3653-3656.2003
Email
[email protected]
Published
2003-11-00
Pages
3653-6
Language
English
Region
United States
NLM ID
0315061
PMCID
PMC253790
Subset
IM
Databases
GENBANK
AY265353
External Links
PubMed source DOI: 10.1128/AAC.47.11.3653-3656.2003 PMC Full Text View journal details
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