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Title: Some effects of steroids on Candida albicans
Author: Wulkau, Susan E.
Awarding Body: Loughborough University
Current Institution: Loughborough University
Date of Award: 1984
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The effect of several bile salts and hydrocortisone, on Candida albicans was investigated. Deoxycholic acid salt, cholic acid salt and glycodeoxycholic acid salt were found to suppress growth at concentrations of 0.1% and above. 3-0-hemisuccinoyldeoxycholic acid salt and hydrocortisone were only slightly inhibitory and glycocholic acid salt and 3-0-hemisuccinoylcholic acid salt had no effect on growth rate. No zones of inhibition were caused by several bile salt derivates - 3 α -succinoy- 7α - hydroxy- 5β -cholan-24-oic acid disodium salt, disodium-3α -sulphoxy-5 β -cholan-24-oic acid, disodium-3α---succinoy-5β -cholan-24-oate, lithocholic acetate sodium salt or methyl-3α-succinoy-5β cholan-24- oate sodium salt. Several of the bile salts were found to cause alterations in morphology which included swelling of some cells, pinching off of portions of hyphae to form chains of cells, and wrinkling of the cell surface. Transmission electron microscopy revealed that cholic acid salt caused more vacuoles in the cytoplasm, and convolutions of some portions of cell membrane. Growth in 0.2% cholic acid salt caused an alteration in sterol content, for example an increase in calciferol, 24,28, dehydroergosterol and 4,4,dimethylzymosterol, and a decrease in ergosterol, lanosterol and squalene. Cholic acid salt caused alterations in fatty acid composition which included an increase in palmitoleate, stearate, and oleate, and a decrease in linoleate and linolenate. The changes in composition were presumed to be in order to maintain the fluidity of the membrane. Cholic acid salt did not damage the cell membrane resulting in leakage, or have any effect on oxygen utilization. The incorporation of sugars into the cell walls of C. albicans was affected by cholic acid salt. The uptake of glucose into cells was unaffected, but its incorporation into cell walls was suppressed. The uptake and incorporation of glucosamine was enhanced at 0.4% cholic acid salt, and mannose incoporation was osuppressed at 0.2% and at 0.4% both mannose uptake and incorporation was suppressed. C. albicans grown in the presence of cholic acid salt was less able to adhere to animal cells than control C. albicans, although the presence of cholic acid salt did not directly suppress adherence. Several of the steroids interacted with commonly used antifungal agents: cholic acid salt and amphotericin B had a synergistic effect, clotrimazole antagonized the effect of deoxycholic acid salt, chenodeoxycholic acid, and hyocholic acid. Miconazole antagonized hydeoxycholic acid, and amphotericin B antagonized hyocholic acid. Hemisuccinoyldeoxycholic acid and amphotericin B antagonized each other.
Supervisor: Not available Sponsor: Science and Engineering Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available