Maria Hadjifrangiskou, Ph.D.

Associate Professor

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Faculty Appointments
Associate Professor of Pathology, Microbiology and Immunology Associate Professor of Urology
Ph.D., MICRO AND MOLECULAR GENETICS, University of Texas Health Science Center, Houston, TexasB.S., Clarion University of Pennsylvania, Clarion, Pennsylvania
Office Address
Vanderbilt University School of Medicine
Dept of Pathology, Microbiology and Immunology-5th Fl
MCN A-5301
Nashville, TN 37232
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.
Research Keywords
We study how bacteria that cause urinary tract infections sense and respond to signals in their environment. Follow Dr. H. on Twitter: @BacterialTalk
Abana CM, Brannon JR, Ebbott RA, Dunigan TL, Guckes KR, Fuseini H, Powers J, Rogers BR, Hadjifrangiskou M. Characterization of blue light irradiation effects on pathogenic and nonpathogenic Escherichia coli. Microbiologyopen [print-electronic]. 2017 Aug; 6(4): PMID: 28332311, PMCID: PMC5552948, DOI: 10.1002/mbo3.466, ISSN: 2045-8827.

Behr S, Kristoficova I, Witting M, Breland EJ, Eberly AR, Sachs C, Schmitt-Kopplin P, Hadjifrangiskou M, Jung K. Identification of a High-Affinity Pyruvate Receptor in Escherichia coli. Sci Rep. 2017 May 5/3/2017; 7(1): 1388. PMID: 28469239, PMCID: PMC5431176, PII: 10.1038/s41598-017-01410-2, DOI: 10.1038/s41598-017-01410-2, ISSN: 2045-2322.

Breland EJ, Zhang EW, Bermudez T, Martinez CR, Hadjifrangiskou M. The histidine residue of QseC is required for canonical signaling between QseB and PmrB in uropathogenic Escherichia coli. J. Bacteriol [print-electronic]. 2017 Apr 4/10/2017; PMID: 28396353, PII: JB.00060-17, DOI: 10.1128/JB.00060-17, ISSN: 1098-5530.

Guckes KR, Breland EJ, Zhang EW, Hanks SC, Gill NK, Algood HM, Schmitz JE, Stratton CW, Hadjifrangiskou M. Signaling by two-component system noncognate partners promotes intrinsic tolerance to polymyxin B in uropathogenic Escherichia coli. Sci Signal. 2017 Jan 1/10/2017; 10(461): PMID: 28074004, PII: 10/461/eaag1775, DOI: 10.1126/scisignal.aag1775, ISSN: 1937-9145.

Breland EJ, Eberly AR, Hadjifrangiskou M. An Overview of Two-Component Signal Transduction Systems Implicated in Extra-Intestinal Pathogenic E. coli Infections. Front Cell Infect Microbiol. 2017; 7: 162. PMID: 28536675, PMCID: PMC5422438, DOI: 10.3389/fcimb.2017.00162, ISSN: 2235-2988.

Shaffer CL, Zhang EW, Dudley AG, Dixon BR, Guckes KR, Breland EJ, Floyd KA, Casella DP, Algood HM, Clayton DB, Hadjifrangiskou M. Purine Biosynthesis Metabolically Constrains Intracellular Survival of Uropathogenic Escherichia coli. Infect. Immun [electronic-print]. 2017 Jan; 85(1): PMID: 27795353, PMCID: PMC5203662, PII: IAI.00471-16, DOI: 10.1128/IAI.00471-16, ISSN: 1098-5522.

Varga MG, Shaffer CL, Sierra JC, Suarez G, Piazuelo MB, Whitaker ME, Romero-Gallo J, Krishna US, Delgado A, Gomez MA, Good JA, Almqvist F, Skaar EP, Correa P, Wilson KT, Hadjifrangiskou M, Peek RM. Pathogenic Helicobacter pylori strains translocate DNA and activate TLR9 via the cancer-associated cag type IV secretion system. Oncogene [print-electronic]. 2016 Dec 12/1/2016; 35(48): 6262-9. PMID: 27157617, PMCID: PMC5102820, PII: onc2016158, DOI: 10.1038/onc.2016.158, ISSN: 1476-5594.

Floyd KA, Mitchell CA, Eberly AR, Colling SJ, Zhang EW, DePas W, Chapman MR, Conover M, Rogers BR, Hultgren SJ, Hadjifrangiskou M. The UbiI (VisC) Aerobic Ubiquinone Synthase Is Required for Expression of Type 1 Pili, Biofilm Formation, and Pathogenesis in Uropathogenic Escherichia coli. J. Bacteriol [electronic-print]. 2016 Oct 10/1/2016; 198(19): 2662-72. PMID: 27161114, PMCID: PMC5019064, PII: JB.00030-16, DOI: 10.1128/JB.00030-16, ISSN: 1098-5530.

Shaffer CL, Good JA, Kumar S, Krishnan KS, Gaddy JA, Loh JT, Chappell J, Almqvist F, Cover TL, Hadjifrangiskou M. Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens. MBio. 2016 Apr 4/26/2016; 7(2): e00221-16. PMID: 27118587, PMCID: PMC4850256, PII: mBio.00221-16, DOI: 10.1128/mBio.00221-16, ISSN: 2150-7511.

Brannon JR, Hadjifrangiskou M. The arsenal of pathogens and antivirulence therapeutic strategies for disarming them. Drug Des Devel Ther. 2016; 10: 1795-806. PMID: 27313446, PMCID: PMC4890686, PII: dddt-10-1795, DOI: 10.2147/DDDT.S98939, ISSN: 1177-8881.

Floyd KA, Meyer AE, Nelson G, Hadjifrangiskou M. The yin-yang driving urinary tract infection and how proteomics can enhance research, diagnostics, and treatment. Proteomics Clin Appl [print-electronic]. 2015 Dec; 9(11-12): 990-1002. PMID: 26255866, DOI: 10.1002/prca.201500018, ISSN: 1862-8354.

Floyd KA, Moore JL, Eberly AR, Good JA, Shaffer CL, Zaver H, Almqvist F, Skaar EP, Caprioli RM, Hadjifrangiskou M. Adhesive fiber stratification in uropathogenic Escherichia coli biofilms unveils oxygen-mediated control of type 1 pili. PLoS Pathog. 2015 Mar; 11(3): e1004697. PMID: 25738819, PMCID: PMC4349694, PII: PPATHOGENS-D-14-02041, DOI: 10.1371/journal.ppat.1004697, ISSN: 1553-7374.

Nagamatsu K, Hannan TJ, Guest RL, Kostakioti M, Hadjifrangiskou M, Binkley J, Dodson K, Raivio TL, Hultgren SJ. Dysregulation of Escherichia coli a-hemolysin expression alters the course of acute and persistent urinary tract infection. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Feb 2/24/2015; 112(8): E871-80. PMID: 25675528, PMCID: PMC4345586, PII: 1500374112, DOI: 10.1073/pnas.1500374112, ISSN: 1091-6490.

Greene SE, Pinkner JS, Chorell E, Dodson KW, Shaffer CL, Conover MS, Livny J, Hadjifrangiskou M, Almqvist F, Hultgren SJ. Pilicide ec240 disrupts virulence circuits in uropathogenic Escherichia coli. MBio. 2014; 5(6): e02038. PMID: 25352623, PMCID: PMC4217179, PII: mBio.02038-14, DOI: 10.1128/mBio.02038-14, ISSN: 2150-7511.

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 [print-electronic]. 2013 Oct 10/8/2013; 110(41): 16592-7. PMID: 24062463, PMCID: PMC3799328, PII: 1315320110, DOI: 10.1073/pnas.1315320110, ISSN: 1091-6490.

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. 2013 Apr; 3(4): a010306. PMID: 23545571, PMCID: PMC3683961, PII: 3/4/a010306, DOI: 10.1101/cshperspect.a010306, ISSN: 2157-1422.

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. 2013; 4(5): e00645-13. PMID: 24023384, PMCID: PMC3774191, PII: mBio.00645-13, DOI: 10.1128/mBio.00645-13, ISSN: 2150-7511.

Kostakioti M, Hultgren SJ, Hadjifrangiskou M. Molecular blueprint of uropathogenic Escherichia coli virulence provides clues toward the development of anti-virulence therapeutics. Virulence [print-electronic]. 2012 Nov 11/15/2012; 3(7): 592-4. PMID: 23154288, PMCID: PMC3545937, PII: 22364, DOI: 10.4161/viru.22364, ISSN: 2150-5608.

Hadjifrangiskou M, Gu AP, Pinkner JS, Kostakioti M, Zhang EW, Greene SE, Hultgren SJ. Transposon mutagenesis identifies uropathogenic Escherichia coli biofilm factors. J. Bacteriol [print-electronic]. 2012 Nov; 194(22): 6195-205. PMID: 22984258, PMCID: PMC3486386, PII: JB.01012-12, DOI: 10.1128/JB.01012-12, ISSN: 1098-5530.

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 [print-electronic]. 2012 Aug; 80(8): 2826-34. PMID: 22665375, PMCID: PMC3434567, PII: IAI.00283-12, DOI: 10.1128/IAI.00283-12, ISSN: 1098-5522.

Hadjifrangiskou M, Hultgren SJ. What does it take to stick around? Molecular insights into biofilm formation by uropathogenic Escherichia coli. Virulence [print-electronic]. 2012 May 5/1/2012; 3(3): 231-3. PMID: 22546905, PMCID: PMC3442832, PII: 19763, DOI: 10.4161/viru.19763, ISSN: 2150-5608.

Hadjifrangiskou M, Kostakioti M, Hultgren SJ. Antitoxins: therapy for stressed bacteria. Nature chemical biology. 2011 Jun; 7(6) Sect. 345,7.

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 [print-electronic]. 2011 Jun; 80(6): 1516-29. PMID: 21542868, PMCID: PMC3643513, DOI: 10.1111/j.1365-2958.2011.07660.x, ISSN: 1365-2958.

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 [print-electronic]. 2009 Sep; 73(6): 1020-31. PMID: 19703104, PMCID: PMC2963169, PII: MMI6826, DOI: 10.1111/j.1365-2958.2009.06826.x, ISSN: 1365-2958.

Hadjifrangiskou M, Koehler TM. Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters. Microbiology (Reading, Engl.). 2008 Aug; 154(Pt 8): 2501-12. PMID: 18667583, PMCID: PMC4225132, PII: 154/8/2501, DOI: 10.1099/mic.0.2007/016162-0, ISSN: 1350-0872.

Hadjifrangiskou M, Chen Y, Koehler TM. The alternative sigma factor sigmaH is required for toxin gene expression by Bacillus anthracis. J. Bacteriol [print-electronic]. 2007 Mar; 189(5): 1874-83. PMID: 17189374, PMCID: PMC1855707, PII: JB.01333-06, DOI: 10.1128/JB.01333-06, ISSN: 0021-9193.