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Department of Pathology, Microbiology, and Immunology

 

 

Maria Hadjifrangiskou, Ph.D.

 

 

Assistant Professor

Dept. of Pathology, Microbiology and Immunology

 

 

Contact Information

 

 

Office Location:
MCN A-5217A

Phone: 615-322-4851

Lab Tech Office: MCN A-5225C, Phone:  615-322-4649

Lab Location:  MCN A-5225, MCN A-5225A, MCN A-5225B

Lab Website:  http://my.vanderbilt.edu/hadjifrangiskoulab/
E-mail: maria.hadjifrangiskou@vanderbilt.edu

 

Campus Mail address:

Pathology, Microbiology and Immunology-5th Fl

MCN A-5301 (2363)

 

US Mailing address:
Vanderbilt University School of Medicine
Dept of Pathology, Microbiology and Immunology-5th Fl
MCN A-5301

Nashville, TN 37232-2363

 


 

 

Research Keywords

 

 

virulence gene regulation, signal transduction, host-pathogen interactions

 

 

Research Description

 

 

Urinary tract infections (UTIs) are among the most frequent bacterial infections, are highly prevalent among women and have a high degree of recurrence. Currently, antibiotics are the primary treatment option for UTI, however they oftentimes fail to eliminate infection, they perturb the host microbiota and select for increased antibiotic resistance. This means that there is a pressing need for the development of alternative strategies for preventing and/or treating UTIs. Uropathogenic Escherichia coli (UPEC), which causes 85% of all UTIs, has evolved a remarkable mechanism to evade host immune defenses and establish infection, by forming biofilm-like intracellular bacterial communities (IBC) inside bladder cells, in addition to forming extracellular biofilms on host cell surfaces and on catheter implants. My lab is interested in identifying factors and mechanisms that regulate UPEC biofilm formation and that could serve as new drug targets. We have performed a screen that has identified 41 such factors, including the QseBC signal transduction system, which we are currently characterizing in more detail. To do this, we use a wide variety of approaches, including molecular biology, cell-based and in vitro assays, chemical biology and 3 mouse models of UTI. Another focus of the lab is to understand the mechanism by which rationally designed small molecules act against UPEC pathogenesis. These small molecular weight inhibitors were initially designed to block pilus assembly, thereby impeding bacterial adherence to biotic and abiotic surfaces; we have come to discover that these molecules impact UPEC gene expression, causing pleiotropic effects on virulence gene regulation and inhibiting biofilm formation. In collaboration with labs at Washington University in Saint Louis and Umea University in Sweden, we are working towards understanding how these inhibitors function and how they can be optimized for use as treatments against UTIs.

 

 

Publications

 

 

Guckes, KR, Kostakioti, M, Breland, EJ, Gu, AP, Shaffer, CL, Martinez, CR, Hultgren, SJ, Hadjifrangiskou, M. Strong cross-system interactions drive the activation of the QseB response regulator in the absence of its cognate sensor. Proc Natl Acad Sci U S A, 110(41), 16592-7, 2013

Hung, C, Zhou, Y, Pinkner, JS, Dodson, KW, Crowley, JR, Heuser, J, Chapman, MR, Hadjifrangiskou, M, Henderson, JP, Hultgren, SJ. Escherichia coli biofilms have an organized and complex extracellular matrix structure. MBio, 4(5), e00645-13, 2013

Kostakioti, M, Hadjifrangiskou, M, Hultgren, SJ. Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harb Perspect Med, 3(4), 2013

Hadjifrangiskou, M, Gu, AP, Pinkner, JS, Kostakioti, M, Zhang, EW, Greene, SE, Hultgren, SJ. "Transposon mutagenesis identifies uropathogenic Escherichia coli biofilm factors&quot. J Bacteriol, 2012

Kostakioti, M, Hultgren, SJ, Hadjifrangiskou, M. Molecular blueprint of uropathogenic Escherichia coli virulence provides clues toward the development of anti-virulence therapeutics. Virulence, 3(7), 2012

Kostakioti, M, Hadjifrangiskou, M, Cusumano, CK, Hannan, TJ, Janetka, JW, Hultgren, SJ. Distinguishing the contribution of type 1 pili from that of other QseB-misregulated factors when QseC is absent during urinary tract infection. Infect Immun, 2012

Hadjifrangiskou, M, Hultgren, S. What does it take to stick around?: Molecular insights into biofilm formation by uropathogenic Escherichia coli. Virulence, 3(3), 2012

Hadjifrangiskou, M, Kostakioti, M, Hultgren, SJ. Antitoxins: therapy for stressed bacteria. Nat Chem Biol, 7(6), 345-7, 2011

Hadjifrangiskou, M, Kostakioti, M, Chen, SL, Henderson, JP, Greene, SE, Hultgren, SJ. A central metabolic circuit controlled by QseC in pathogenic Escherichia coli. Mol Microbiol, 80(6), 1516-29, 2011

Kostakioti, M, Hadjifrangiskou, M, Pinkner, JS, Hultgren, SJ. QseC-mediated dephosphorylation of QseB is required for expression of genes associated with virulence in uropathogenic Escherichia coli. Mol Microbiol, 73(6), 1020-31, 2009

Hadjifrangiskou, M, Koehler, TM. Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters. Microbiology, 154(Pt 8), 2501-12, 2008

Hadjifrangiskou, M, Chen, Y, Koehler, TM. The alternative sigma factor sigmaH is required for toxin gene expression by Bacillus anthracis. J Bacteriol, 189(5), 1874-83, 2007