Vanderbilt University School of Medicine

Hadjifrangiskou, Maria , Ph.D.
Assistant Professor of Pathology, Microbiology and Immunology

Lab Url: http://my.vanderbilt.edu/hadjifrangiskoulab/

Phone Number: 615-322-4851

Email Address:maria.hadjifrangiskou@vanderbilt.edu

Hadjifrangiskou, Maria's picture

Office Address   Mailing Address

A-5225A MCN

Vanderbilt University School of Medicine Dept of Pathology, Microbiology and Immunology-5th Fl 37232


Research Keywords
virulence gene regulation, signal transduction, host-pathogen interactions,Infectious disease,Signal transduction

Research Specialty
We study virulence mechanisms of bacterial pathogens causing urinary tract infections

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.

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

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.

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.

Hadjifrangiskou, M, Kostakioti, M, Hultgren, SJ. Antitoxins: therapy for stressed bacteria. Nat Chem Biol, 7(6), 345-7, 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. PMCID:2963169

Hadjifrangiskou, M, Koehler, TM. Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters. Microbiology, 154(Pt 8), 2501-12, 2008. PMCID:2963169

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. PMCID:1855707


Postdoctoral Position Available
No

Postdoctoral Position Details
N/A

Updated Date
01/06/2014



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