geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole


, : Identification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporter-encoding gene, CnAFR1, involved in the resistance to fluconazole. Molecular Microbiology 47(2): 357-371

Resistance to fluconazole is a possible event during prolonged suppressive drug therapy for cryptococ-cal meningitis, the most frequently encountered life-threatening manifestation of cryptococcosis. The knowledge of this resistance at the molecular level is important for management of cryptococcosis. In order to identify genes involved in azole resistance in Cryptococcus neoformans, a cDNA subtraction library technique was chosen as a strategy. First, a fluconazole-resistant mutant BPY22.17 was obtained from a susceptible clinical isolate BPY22 by in vitro exposure to the drug. Then, a subtractive hybridization procedure was used to compare gene expression between the obtained strains. We identified a cDNA overexpressed in the fluconazole-resistant strain BPY22.17 that was used as a probe to isolate the entire gene in a C. neoformans genomic library. Sequence analysis of this gene identified an ATP Binding Cassette (ABC) transporter-encoding gene called C. neoformans AntiFungal Resistance 1 (CnAFR1). Disruption of CnAFR1 gene in the resistant isolate (BPY22.17) resulted in an enhanced susceptibility of the knock-out mutant cnafr1 against fluconazole, whereas reintroduction of the gene in cnafr1 resulted in restoration of the resistance phenotype, thus confirming that CnAFR1 is involved in fluconazole resistance of C. neoformans. Our findings therefore reveal that an active drug efflux mechanism can be involved in the development of azole resistance in this important human pathogen.

US$19.90

PMID: 12519188

DOI: 10.1046/j.1365-2958.2003.03281.x


Other references

Sokolov, B.P., 1980: Comparative study of the proteins of influenza virus type A nucleoproteins. A comparative study of protein of nucleoproteins (NP-protein) of influenza A viruses by peptide mapping shows its variability to be small within one drifting series and quite marked in strains belonging to different sero-types. In oligopeptide map...

Klein, J.J.; Mondozzi, M.A.; Andrews, D.A., 2008: The need for a juvenile fire setting database. A juvenile fire setter can be classified as any youth setting a fire regardless of the reason. Many communities have programs to deal with this problem, most based on models developed by the United States Fire Administration. We reviewed our progr...

Metzmacher, M., 1989: La Reserve naturelle des Hautes-Fagnes deviendra-t-elle un observatoire geo-biosphere? 3. Apercu de l'evolution de l'avifaune dans la Reserve naturelle des Hautes-Fagnes: le cas de la fauvette des jardins (Sylvia borin) et de la fauvette grisette (Sylvia communis). Hautes Fagnes, 551: 13-16

Rhodes, L.L.; Syhre, M., 1995: Okadaic acid production by a New Zealand Prorocentrum lima isolate. Cells of Prorocentrum lima, isolated from sediments collected from Rangaunu Harbour, P. lima (a Spanish isolate), and P. compressum, isolated from wrack collected at Ninety Mile Beach. Northland, New Zealand, were cultured and analysed for okadaic...

Bangu, N.T.A.; Chove, B.E.; Nnko, S.A.M.; Gidamis, A.B., 1999: Particle size distribution in milled sorghum grains of different corneousness. The particle size distribution of milled samples of three varieties of sorghum [Sorghum bicolor (L) Moench] coded V3, V6 and V8 was determined by sieve analysis. The moisture content of the grains ranged between 9.83 and 10.60%, wet weight basis....

Hennig F.; Brandl M.; Link W.; Carbon R., 1986: Recovery of representative bacteriological material at secondary pneumonia three lumen catheter according to wimberley in comparison with the secretion aspirated by bronchoscopy. Successful therapy of secondary pneumonia calls for the specific use of antibiotics. In the case of seriously ill or artificially respirated patients, the recovery of respresentative bacteriological material from the lower pulmonary segments is pa...

Liao, C-Ta.; Lin, C-Yu.; Fan, K-Hsing.; Hsueh, C.; Lee, L-Yu.; Wang, H-Ming.; Huang, S-Fu.; Chen, I-How.; Kang, C-Jan.; Ng, S-Hang.; Lin, C-Hung.; Huang, Y-Chen.; Yen, T-Chen., 2013: Outcome analyses of unusual site neck recurrence in oral cavity cancer. To understand the frequency, clinical significance, and benefits of salvage therapy in oral cavity squamous cell carcinoma (OSCC) patients with regional nodal recurrence at unusual sites (prelaryngeal area, parotid area, and retropharyngeal area)....

Cudd, T.A.; Chen, W.J.ng A.; West, J.R., 2001: Fetal and maternal sheep hypothalamus pituitary adrenal axis responses to chronic binge ethanol exposure during the third trimester equivalent. Background: We tested the hypothesis that in utero ethanol exposure results in changes in fetal and maternal adrenocorticotropin (ACTH) and cortisol during the third trimester equivalent, by using a chronically instrumented fetal sheep model. Meth...

Bauermeister, Jé.J.; Puente, Aíbal.; Martínez, Jé.V.; Cumba, E.; Scándar, Rén.O.; Bauermeister, Jé.A., 2011: Parent perceived impact of Spaniard boys' and girls' inattention, hyperactivity, and oppositional defiant behaviors on family life. This study examined the impact of inattention, hyperactivity, and oppositional defiant disorder (ODD) behaviors and gender on family life. We created scales for the Family Experiences Inventory (FEI) in a nonclinical sample of Spaniard families wi...

Cavagnero, S.; Nishimura, C.; Schwarzinger, S., 2001: Conformational and dynamic characterization of the molten globule state of an apomyoglobin mutant with an altered folding pathway. Kinetic and equilibrium studies of apomyoglobin folding pathways and intermediates have provided important insights into the mechanism of protein folding. To investigate the role of intrinsic helical propensities in the apomyoglobin folding proces...