Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


case1205848497.pdf (1.38 MB)

ETD Abstract Container

Abstract Header

STUDIES ON THE VIRULENCE PROPERTIES AND REGULATION OF THE CorA MAGNESIUM CHANNEL

Papp-Wallace, Krisztina Margaret
http://rave.ohiolink.edu/etdc/view?acc_num=case1205848497

Abstract Details

2008, Doctor of Philosophy, Case Western Reserve University, Pharmacology.
CorA is the primary Mg2+ channel in Salmonella enterica serovar Typhimurium.A strain lacking corA is attenuated in mice after infection either by oral gavage or intraperitoneal injection. Microarray studies show that several virulence effectors in Salmonella pathogenicity island 1 and Salmonella pathogenicity island 2 are repressed in the corA strain compared to wild type. While these results could be sufficient to explain the virulence deficit, the microarray data suggest additional defects that could also contribute. Motility is significantly reduced in a corA strain whereas enterochelin-dependent iron uptake and curli are upregulated. A corA strain is defective for invasion of and replication within Caco-2 epithelial cells. However, a corA strain does not have a significant survival defect in J774A.1 macrophages. Thus, despite the presence of two other Mg2+ transporters, loss of CorA affects multiple systems which manifests ultimately as a decrease in virulence. We further examined Salmonella interaction with Caco-2 epithelial cells. Inhibiting CorA acutely or chronically with a high concentration of a selective inhibitor, cobalt (III) hexaammine, had no effect on S. Typhimurium invasion of and replication within Caco-2 epithelial cells. Complementing the corA mutation with a corA from various species rescued the invasion defect only if the complementing allele was functional and if it was evolutionarily similar to S. Typhimurium CorA. One explanation for these results could be that regulation of CorA function is needed for optimal virulence. Further experiments examining corA transcription, CorA protein content, CorA transport, and Mg2+ content indicated that both CorA expression and CorA function are differentially regulated. Moreover the rates of Mg2+ influx via CorA are not strictly correlated with either protein levels or Mg2+ content. We conclude that loss of the CorA protein disrupts a regulatory network(s) with the ultimate phenotype of decreased virulence. This conclusion is compatible with the microarray results which showed that loss of corA resulted in changes in transcription in multiple metabolic pathways. Further study of the regulation of CorA expression and function provides an opportunity to dissect the complexity of Mg2+ homeostasis and its ties to virulence within the bacterium.
Michael Maguire (Advisor)
John Mieyal (Committee Chair)
Anthony Berdis (Committee Member)
Arne Rietsch (Committee Member)
George Dubyak (Committee Member)
225 p.
Microbiology
Salmonella; magnesium; transport; virulence

Recommended Citations

Citations

  • Papp-Wallace, K. M. (2008). STUDIES ON THE VIRULENCE PROPERTIES AND REGULATION OF THE CorA MAGNESIUM CHANNEL [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1205848497

    APA Style (7th edition)

  • Papp-Wallace, Krisztina. STUDIES ON THE VIRULENCE PROPERTIES AND REGULATION OF THE CorA MAGNESIUM CHANNEL. 2008. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1205848497.

    MLA Style (8th edition)

  • Papp-Wallace, Krisztina. "STUDIES ON THE VIRULENCE PROPERTIES AND REGULATION OF THE CorA MAGNESIUM CHANNEL." Doctoral dissertation, Case Western Reserve University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1205848497

    Chicago Manual of Style (17th edition)

case1205848497
1,130
© 2008, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.