Date of Award

1996

Degree Name

Biological Sciences

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Byran Larsen

Second Advisor

Susan Jackman

Third Advisor

Todd Green

Fourth Advisor

Michael Moore

Fifth Advisor

Donald Primerano

Sixth Advisor

Leonard J. Deutsch

Abstract

Changes in the balance between commensal microbes and mammalian hosts can cause disease if the scales tip in favor of the microbe. Although usually caused by a defective host immune response, overgrowth of or changes in the microbe may also be responsible for opportunistic infections. Clinical and laboratory investigations have indicated that mammalian hormones, including estrogen, can influence the production of symptomatic disease and the virulence attributes of Candida albicans.

This study demonstrated enhanced growth of some strains of C. albicans when 17β-estradiol was added to the growth medium. Measurement of extracellular protein under the influence of estradiol did not parallel the growth study results when corrected for the number of viable cells. Investigation of the effect of steroidal hormones on germ tube production, a putative virulence factor, showed no significant stimulation by any hormone. However, estradiol did induce four of the six strains to germinate more than their controls without hormone. The strains were variable in their innate tendency to germinate and in their response to steroidal hormones. Estrogen can protect mammalian cells from thermal stress suggesting a study of estradiol’s effect on the survival of C. albicans strains after exposure to 50°C for 15 minutes. Estrogen provided significant protection in four of the six strains tested. Each of these four strains showed significant suppression of acid proteinase secretion when grown 48 hours with estradiol when enzyme activity was corrected for cell number. Since C. albicans has a cytosolic estrogen-binding protein, we looked for genetic evidence of a structural homologue of the mammalian estrogen receptor. Southern blot analyses were performed on the genome of a C. albicans strain that had shown growth stimulation from 17β-estradiol using a 1.9kb fragment of the human estrogen receptor (hER) as a probe. No hybridization was detected under low or high stringency conditions. PCR was performed using primers based on a highly conserved portion of the hER with yeast genomic DNA as a template. No product was detected. The variability in response to estrogen between Candida albicans strains may be due to metabolic differences, genetic differences or structural differences. Although the mechanism of estradiol growth stimulation is unclear, such stimulation could have an influence on pathogenicity and therefore deserves additional investigation.

Subject(s)

Candida albicans.

Estrogen.

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