Isolation and characterization of echinocandin resistant Candida albicans mutants
| dc.contributor.author | Friesen, Mark Henry | en_US |
| dc.date.accessioned | 2007-05-15T15:25:58Z | |
| dc.date.available | 2007-05-15T15:25:58Z | |
| dc.date.issued | 1997-04-01T00:00:00Z | en_US |
| dc.degree.discipline | Pharmacy | en_US |
| dc.degree.level | Master of Science (M.Sc.) | en_US |
| dc.description.abstract | LY303366 (LY) is an investigational echinocandin that has demonstrated activity against Candida species. We attempted to isolate an LY resistant mutant by plating the C. albicans clinical strain Y41 at a concentration of 10$\sp7$ CFU/plate on Brain Heart Infusion agar (BHI) plates supplemented with LY at concentrations of 1 to 40 $\mu$g/ml. After 7 days of incubation at 35$\sp\circ$C very small colonies were observed. One colony was selected and repeatedly subcultured on BHI with 1 $\mu$g/ml LY. After 5 passages the MIC was demonstrated to be 1.28 $\mu$g/ml LY, (wild type MIC = 0.04 $\mu$g/ml, an increase of 32$\times$). However, when 6 colonies were individually subcultured to Sabouraud dextrose agar (SDA) plates, only 3 remained resistant to LY. One of the transient mutant strains was evaluated in terms of: antifungal susceptibility (amphotericin B, 5-flucytosine, fluconazole, ketoconazole), growth, stability, and pharmacodynamic time-kill curves. There were no differences observed between parent and transient mutant strains in antifungal susceptibility, or growth patterns. Transient resistant strains reverted back to the parent MIC after 3 passages on SDA. The resistance phenotype was restored when this strain was cultured on BHI with 1 $\mu$g/ml LY. The transient resistant strain exhibit regrowth during pharmacodynamic time-kill curves at 1$\times$ MIC of LY after this strain had reverted to the wild type MIC. One of the stable mutant strains was evaluated in terms of: antifungal susceptibility (amphotericin B, 5-flucytosine, fluconazole, ketoconazole), morphology, growth, stability, pharmacodynamic time kill-curves, and germ tube formation. (Abstract shortened by UMI.) | en_US |
| dc.format.extent | 7216387 bytes | |
| dc.format.extent | 184 bytes | |
| dc.format.mimetype | application/pdf | |
| dc.format.mimetype | text/plain | |
| dc.identifier.uri | http://hdl.handle.net/1993/1010 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.title | Isolation and characterization of echinocandin resistant Candida albicans mutants | en_US |
| dc.type | master thesis | en_US |