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Karen A. Skorupski, PhD

Associate Professor of Microbiology and Immunology

Microbiology and Immunology

Rutgers - The State University, Ph.D ., 1988
University of New Haven, B.S., 1982
University of New Haven, A.S., 1980

After postdoctoral work at the DuPont Merck Pharmaceutical Company and in the Department of Microbiology at Dartmouth Medical School, Dr. Skorupski joined the faculty of the Department of Microbiology at Dartmouth Medical School in 1997.


Contact Information:

Dartmouth Medical School
Vail Building - HB 7550
Hanover NH 03755

Phone: 603-650-1623
Fax: 603-650-1318
Email: Karen.A.Skorupski@Dartmouth.EDU

Professional Interests:

Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. We are interested in the regulation of virulence gene expression during V. cholerae infection. Toxigenic strains of V. cholerae possess two distinct phage derived pathogenicity islands, VPI which encodes the toxin-coregulated pilus (TCP), an essential colonization factor, and CTX which encodes cholera toxin (CT). We have recently identified two new transcriptional regulators, AphA and AphB, which function synergistically to activate the expression of TCP and CT by activating the expression of a membrane bound transcriptional activator, TcpP, which is encoded on the VPI. AphA appears to be a novel type of transcriptional activator with no known homologs and AphB is a member of the LysR family. The activation of TcpP by AphA and AphB occurs only under certain environmental conditions and appears to be the initial regulatory step in the virulence transcriptional cascade. Mutants defective for either one of these genes are attenuated in the infant mouse cholera model. Interestingly, AphA and AphB are not themselves encoded on the VPI or CTX elements but are located in regions of the V. cholerae chromosome not previously associated with pathogenesis. Thus, these proteins are likely to play a role in normal cellular physiology and function to couple physiological responses with virulence gene expression. We are utilizing a combination of genetic and biochemical approaches to elucidate the mechanism of AphA and AphB mediated transcriptional activation of tcpP and to understand how these two proteins couple environmental conditions to the expression of virulence genes. Since LysR regulators are known to require small molecule coinducers present under certain conditions to activate gene expression, it is hoped that these studies will lead to the identification of new targets for antimicrobial design.

Selected Publications:


Structural basis for virulence regulation in Vibrio cholerae by unsaturated fatty acid components of bile.
Cruite JT, Kovacikova G, Clark KA, Woodbrey AK, Skorupski K, Kull FJ
Commun Biol. 2019;2:440. doi: 10.1038/s42003-019-0686-x. Epub 2019 Nov 28.
PMID: 31815195

Identification of a Small Molecule Activator for AphB, a LysR-Type Virulence Transcriptional Regulator in Vibrio cholerae.
Privett BR, Pellegrini M, Kovacikova G, Taylor RK, Skorupski K, Mierke D, Kull FJ
Biochemistry. 2017 Jul 25;56(29):3840-3849. doi: 10.1021/acs.biochem.7b00337. Epub 2017 Jul 11.
PMID: 28640592

Bile salts and alkaline pH reciprocally modulate the interaction between the periplasmic domains of Vibrio cholerae ToxR and ToxS.
Midgett CR, Almagro-Moreno S, Pellegrini M, Taylor RK, Skorupski K, Kull FJ
Mol Microbiol. 2017 Jul;105(2):258-272. doi: 10.1111/mmi.13699. Epub 2017 May 17.
PMID: 28464377

The Fatty Acid Regulator FadR Influences the Expression of the Virulence Cascade in the El Tor Biotype of Vibrio cholerae by Modulating the Levels of ToxT via Two Different Mechanisms.
Kovacikova G, Lin W, Taylor RK, Skorupski K
J Bacteriol. 2017 Apr 1;199(7) pii: e00762-16. doi: 10.1128/JB.00762-16. Epub 2017 Mar 14.
PMID: 28115548

Proteolysis of virulence regulator ToxR is associated with entry of Vibrio cholerae into a dormant state.
Almagro-Moreno S, Kim TK, Skorupski K, Taylor RK
PLoS Genet. 2015 Apr;11(4):e1005145. doi: 10.1371/journal.pgen.1005145. Epub 2015 Apr 7.
PMID: 25849031

The 40-residue insertion in Vibrio cholerae FadR facilitates binding of an additional fatty acyl-CoA ligand.
Shi W, Kovacikova G, Lin W, Taylor RK, Skorupski K, Kull FJ
Nat Commun. 2015 Jan 21;6:6032. doi: 10.1038/ncomms7032. Epub 2015 Jan 21.
PMID: 25607896

Characterization of BreR interaction with the bile response promoters breAB and breR in Vibrio cholerae.
Cerda-Maira FA, Kovacikova G, Jude BA, Skorupski K, Taylor RK
J Bacteriol. 2013 Jan;195(2):307-17. doi: 10.1128/JB.02008-12. Epub 2012 Nov 9.
PMID: 23144245

The crystal structure of AphB, a virulence gene activator from Vibrio cholerae, reveals residues that influence its response to oxygen and pH.
Taylor JL, De Silva RS, Kovacikova G, Lin W, Taylor RK, Skorupski K, Kull FJ
Mol Microbiol. 2012 Feb;83(3):457-70. doi: 10.1111/j.1365-2958.2011.07919.x. Epub 2012 Jan 10.
PMID: 22053934

H-NS binding and repression of the ctx promoter in Vibrio cholerae.
Stonehouse EA, Hulbert RR, Nye MB, Skorupski K, Taylor RK
J Bacteriol. 2011 Feb;193(4):979-88. doi: 10.1128/JB.01343-09. Epub 2010 Dec 17.
PMID: 21169492

The LysR-type virulence activator AphB regulates the expression of genes in Vibrio cholerae in response to low pH and anaerobiosis.
Kovacikova G, Lin W, Skorupski K
J Bacteriol. 2010 Aug;192(16):4181-91. doi: 10.1128/JB.00193-10. Epub 2010 Jun 18.
PMID: 20562308

View more publications on PubMed