My research interests lie in the field of cellular microbiology and are focused on the mechanisms by which bacterial toxins exploit eukaryotic cell processes. Specifically, the long-term objective of my research program is to understand how cholera toxin (CT) enters the eukaryotic cytosol. After CT binds to the plasma membrane of a target cell, it is delivered to the endoplasmic reticulum (ER) by retrograde vesicular transport. The catalytic A1 polypeptide of CT (CTA1) then crosses the ER membrane, enters the cytosol, and initiates the major toxic effects of CT. It is hypothesized that the ER-to-cytosol translocation of CTA1 involves a quality control mechanism known as ER-associated degradation (ERAD). This system recognizes misfolded proteins in the ER and exports them to the cytosol for modification with ubiquitin, which serves as a molecular tag for degradation. A surface-exposed hydrophobic region in CTA1 may trigger ERAD activity and stimulate CTA1 entry into the cytosol; degradation in the cytosol is presumably avoided, at least to some extent, because CTA1 has a paucity of the lysine residues that serve as ubiquitin attachment sites. Other toxins such as ricin and Shiga toxin also move from the cell surface to the ER and are thought to exploit ERAD for passage into the cytosol. We have employed methods in genetics, biochemistry, molecular biology, and cell biology to provide functional evidence for the ERAD model of toxin translocation. These tools will now be applied to tissue culture or yeast model systems in order to dissect the molecular events that allow CT and related toxins to enter the eukaryotic cell.

Recent Publications

1.    Teter K, Jobling MG, and Holmes RK.  Vesicular Transport is not Required for the Cytoplasmic Pool of Cholera Toxin to Interact with the Stimulatory Alpha Subunit of the Heterotrimeric G Protein.  Infect Immun, 2004; 72:6826-6835.

2.    Gorbea C, Goellner GM, Teter K, Holmes RK, and Rechsteiner M.  Characterization of Mammalian ECM29, a 26S Proteasome-Associated Protein That Localizes to the Nucleus and Membrane Vesicles.  J Biol Chem, 2004; 279(52):54849-54861.

3.    Guerra L, Teter K, Lilley BN, Stenerlöw B, Holmes RK, Ploegh HL, Sandvig K, Thelestam M, and Frisan T.  Cellular Internalization of Cytolethal Distending Toxin: a New End to a Known Pathway.  Cell Microbiol, 2005; 7(7):921-934.

4.   Teter K, Jobling MG, Sentz D, and Holmes RK.  The Cholera Toxin A13 Subdomain is Essential for Interaction with ADP-Ribosylation Factor 6 and Full Toxic Activity but Is Not Required for Translocation from the Endoplasmic Reticulum to the Cytosol.  Infect Immun, 2006; 74:2259-2267.

5.   Pande AH, Moe D, Jamnadas M, Tatulian SA, and Teter K.  The Pertussis Toxin S1 Subunit is a Thermally Unstable Protein Susceptible to Degradation by the 20S Proteasome.  Biochemistry, 2006; 45(46):13734-13740.

6.   Navarro-Garcia F, Canizalez-Roman A, Burlingame KE, Teter K, and Vidal JE.  Pet, a Non-AB Toxin, is Retrograde Transported and Translocated into Epithelial Cells.  Infect Immun, 2007; 75(5):2101-2109.

7.   Geden SE, Gardner RA, Fabbrini MS, Ohashi M, Phanstiel O, and Teter K.  Lipopolyamine Treatment Increases the Efficacy of Intoxication with Saporin and an Anti-Cancer Saporin Conjugate.  FEBS J, 2007; 274: 4825-4836.

8.    Pande AH, Scaglione P, Taylor M, Nemec KN, Tuthill S, Moe D, Holmes RK, Tatulian SA, and Teter K.  Conformational Instability of the Cholera Toxin A1 Polypeptide.  J Mol Biol, 2007; 374:1114-1128. 

9.  Scaglione P, Nemec KN, Burlingame KE, Grabon A, Huerta J, Navarro-Garcia F, Tatulian SA, and Teter K.  Structural Characteristics of the Plasmid-Encoded Toxin from Enteroaggregative Escherichia coli.  Biochemistry, 2008; 47(36):9582–9591.

10. Guerra L, Nemec KN, Massey S, Tatulian SA, Thelestam M, Frisan T, and Teter K. A Novel Mode of Translocation for Cytolethal Distending Toxin. Biochim Biophys Acta, 2009; 1793(3):489-495.

11. Quinones B, Massey S, Friedman M, Swimley MS, and Teter K. Novel Cell-Based Method to Detect Shiga Toxin 2 from Escherichia coli O157:H7 and Inhibitors of Toxin Activity. Appl Environ Microbiol, 2009; 75(5):1410-1416.