Michelle Dziejman, Ph.D.

Michelle Dziejman, Ph.D.

Contact Information

University of Rochester
School of Medicine and Dentistry
601 Elmwood Ave., Box 672
Rochester, NY 14642

Office: (585) 273-4459
Lab: (585) 275-0685

Research Bio

Research Focus
Type Three Secretion System mediated pathogenesis of V. cholerae
Research Overview
Vibrio cholerae is a diverse species found in aquatic environments worldwide, and it is the causative agent of the severe diarrheal disease known as cholera. Epidemic disease in Asia and South America is currently caused only by strains of the O1 or O139 serogroup of V. cholerae. However, a significant amount of world wide, sporadic disease is caused by strains of other serogroups, collectively called non-O1/non-O139 strains. Ribotyping and comparative genomic analyses have shown that these strains are very diverse both phylogenetically and in their genetic content compared to strains of the O1 and O139 serogroups. Unlike epidemic strains, the majority of non-O1/non-O139 strains do not carry the well characterized virulence factors for colonization (toxin co-regulated pilus, TCP) and cholera toxin (CT) production. It is presumed that pathogenic non-O1/non-O139 isolates have acquired novel virulence factors that confer the ability to colonize and cause disease in a TCP/CT independent manner. However, these strains remain largely uncharacterized.
AM-19226 is a clinically isolated, O39 serogroup strain of V. cholerae that does not carry the genes encoding TCP or CT. However, whole genome sequencing of AM-19226 has identified open reading frames (ORFs) having significant similarity to genes encoding the structural components of a Type Three Secretion System (T3SS). These ORFs, named vcs, lie within a ~60kb pathogenicity island that has been found in other non-O1/non-O139 strains. A wide variety of gram-negative, pathogenic bacteria use TTSSs as a conserved mechanism to translocate multiple virulence factors, referred to as T3SS effector proteins, directly into the cytosol of eukaryotic cells. We therefore postulate that the vcs genes represent a previously unidentified mechanism for host cell interaction acquired by V. cholerae. Also within this island are two open reading frames predicted to encode proteins having sequence similarity to ToxR, an important player in the network of regulatory proteins that govern the expression of virulence factors in epidemic O1 and O139 serogroup strains. Although the amino acid sequences of proteins encoding the structural components are highly conserved among T3SSs of different organisms, the sequences of effector proteins typically share limited or no homology. Effector proteins are therefore often unique to a specific T3SS, and their interactions with eukaryotic host cell proteins serve to elicit distinct phenotypes beneficial for the particular bacterial pathogen.
In order to understanding the scope of molecular mechanisms responsible for TTSS mediated disease, we are working to:

1. understand the role of the ToxR paralogs and ToxR itself in T3SS related gene expression.
2. identify in vitro conditions that promote expression of the T3SS genes.
3. identify effector proteins that are required during infection to provide functions critical for colonization and disease.

To accomplish these goals we use several experimental approaches, including genetic and molecular techniques complimented by in vitro mammalian cell culture model systems. In addition, we collaborate with Dr. J. Scott Butler (also in the Dept. of Microbiology & Immunology) in using S. cerevisiae as a model system for the identification of effector proteins and the analyses of their molecular interactions with components of the eukaryotic host machinery.

Awards & Honors (National)


Recent Journal Articles

Showing the 5 most recent journal articles. 24 available »

Miller KA, Sofia MK, Weaver JW, Seward CH, Dziejman M. "Regulation by ToxR-Like Proteins Converges on vttRB Expression To Control Type 3 Secretion System-Dependent Caco2-BBE Cytotoxicity in Vibrio cholerae." Journal of bacteriology. 2016 198(11):1675-82. Epub 2016 May 13.
Seward CH, Manzella A, Alam A, Butler JS, Dziejman M. "Using S. cerevisiae as a Model System to Investigate V. cholerae VopX-Host Cell Protein Interactions and Phenotypes." Toxins. 2015 7(10):4099-110. Epub 2015 Oct 14.
Chaand M, Miller KA, Sofia MK, Schlesener C, Weaver JW, Sood V, Dziejman M. "Type 3 Secretion System Island Encoded Proteins Required for Colonization by Non-O1/non-O139 Serogroup V. cholerae." Infection and immunity. 2015 Epub 2015 May 04.
Chaand M, Dziejman M. "Vibrio cholerae VttR(A) and VttR(B) regulatory influences extend beyond the type 3 secretion system genomic island." Journal of bacteriology. 2013 195(10):2424-36. Epub 2013 Mar 22.
Miller KA, Hamilton E, Dziejman M. "The Vibrio cholerae trh gene is coordinately regulated in vitro with type III secretion system genes by VttR(A)/VttR(B) but does not contribute to Caco2-BBE cell cytotoxicity." Infection and immunity. 2012 80(12):4444-55. Epub 2012 Oct 08.

Current Appointments

Associate Professor - Department of Microbiology and Immunology (SMD) - Primary


PhD | Microbiology, All Other | Univ of Pennsylvania1996
BS | Microbiology | University of Rochester1988