Document Detail


Enhanced pathogenicity of Candida albicans pre-treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis.
MedLine Citation:
PMID:  16239285     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: To investigate the relative pathogenicity of Candida albicans treated with subinhibitory concentrations of fluconazole in a mouse model of disseminated candidiasis. Previous studies indicate that these cells secrete 10 times more farnesol than do untreated cells. In our usage, subinhibitory means a concentration which causes a prominent decrease in turbidity but still allows some cell growth. METHODS: C. albicans A72 cells were grown overnight in 0-5.0 microM fluconazole, washed, and inoculated in mice by tail vein injection. Groups of 15 or 16 mice were injected with 1.3 x 10(6) cells and mortality was recorded for 7 days post-inoculation. The levels of farnesol in control and treated C. albicans were determined by GC/MS. RESULTS: The MIC50 for strain A72 was 0.125 mg/L (0.4 microM). Mice administered C. albicans pre-treated with 0.5 to 1.0 microM fluconazole died 2.5 to 4 days earlier and had 2 to 4 times higher mortality rates than mice given untreated C. albicans. Fluconazole (0.5 to 1.0 microM) pre-treated cells were 4.2 to 8.5 times more lethal (P < 0.001) than untreated cells. The extracellular, membrane bound, and intracellular farnesol concentrations of cells pre-treated with 1.0 muM fluconazole were 12-, 2- and 6-times those of untreated cells. CONCLUSIONS: The effects of fluconazole on C. albicans are very concentration-dependent. The enhanced pathogenicity of fluconazole pre-treated C. albicans in mice should be relevant to the therapeutic and prophylactic use of fluconazole. Further research is needed to explore whether farnesol production by C. albicans is a virulence factor.
Authors:
Dhammika H M L P Navarathna; Jacob M Hornby; Natasha Hoerrmann; Anne M Parkhurst; Gerald E Duhamel; Kenneth W Nickerson
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2005-10-20
Journal Detail:
Title:  The Journal of antimicrobial chemotherapy     Volume:  56     ISSN:  0305-7453     ISO Abbreviation:  J. Antimicrob. Chemother.     Publication Date:  2005 Dec 
Date Detail:
Created Date:  2005-12-12     Completed Date:  2006-03-21     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7513617     Medline TA:  J Antimicrob Chemother     Country:  England    
Other Details:
Languages:  eng     Pagination:  1156-9     Citation Subset:  IM    
Affiliation:
School of Biological Sciences, University of Nebraska, Lincoln, NE 68588, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antifungal Agents / pharmacology
Candida albicans / chemistry,  drug effects*,  pathogenicity*
Candidiasis / microbiology*
Disease Models, Animal
Farnesol / metabolism
Fluconazole / pharmacology*
Gas Chromatography-Mass Spectrometry
Mice
Microbial Sensitivity Tests
Survival Analysis
Virulence / drug effects*
Grant Support
ID/Acronym/Agency:
P20 RRO16454/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antifungal Agents; 4602-84-0/Farnesol; 86386-73-4/Fluconazole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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