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HcZrt2, a Zinc Transporter and Nutritional Virulence Determinant in Histoplasma Capsulatum

Dade, Jessica E
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470753451

Abstract Details

2016, PhD, University of Cincinnati, Medicine: Molecular Genetics, Biochemistry, and Microbiology.
Histoplasmosis is a pulmonary fungal infection caused by the inhalation of Histoplasma capsulatum spores, which inhabit bird and bat guano and soil mainly in the Mississippi and Ohio River Valleys. An initial adaptive response to the host environment is the morphological switch to the yeast form triggered by host’s temperature of 37 degrees Celsius. For persistent infection subsequent adaptive responses include modulation of the phagolysosome acidic pH and iron and calcium acquisition. This study focuses on the zinc acquisition mechanism that permits survival in the zinc restrictive environment within activated macrophages. We demonstrated that HcZrt2, one of the three predicted zinc transporters in H. capsulatum, is employed by the organism to acquire zinc. HcZrt2 was selected for functional characterization based on its transcriptional regulation of zinc and sequence similarities to other fungal zinc transporters. Complementation analysis of HcZrt2 in a Saccharomyces cerevisiae lacking zinc transporters confirmed functional similarities to ScZrt1 and ScZrt2. The reduced expression of HcZrt2 transcripts underscored HcZrt2’s role in vitro and in vivo. It is essential for zinc acquisition and growth of H. capsulatum yeasts in zinc deficient media. The loss of HcZrt2 does not inhibit phagocytosis by macrophages; instead it limits the progressive growth of H. capsulatum at the onset of adaptive immunity and attenuates virulence. These studies reveal a zinc homeostatic mechanism that is vital for growth in low zinc environments and essential for virulence.
George Deepe, M.D. (Committee Chair)
David Askew, Ph.D. (Committee Member)
Edmund Choi, Ph.D. (Committee Member)
Gary Dean, Ph.D. (Committee Member)
Bryan Mackenzie, Ph.D. (Committee Member)
Alan Smulian, M.D. (Committee Member)
99 p.
Genetics
Histoplasmosis; Zinc

Recommended Citations

Citations

  • Dade, J. E. (2016). HcZrt2, a Zinc Transporter and Nutritional Virulence Determinant in Histoplasma Capsulatum [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470753451

    APA Style (7th edition)

  • Dade, Jessica. HcZrt2, a Zinc Transporter and Nutritional Virulence Determinant in Histoplasma Capsulatum. 2016. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470753451.

    MLA Style (8th edition)

  • Dade, Jessica. "HcZrt2, a Zinc Transporter and Nutritional Virulence Determinant in Histoplasma Capsulatum." Doctoral dissertation, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1470753451

    Chicago Manual of Style (17th edition)

ucin1470753451
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© 2016, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.