Profile

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  approach we are taking advantage of is imaging mass spectrometry, which has allowed us to discern differential protein profiles within surface-associated biofilms and uncovered complex regulatory cascades that lead to differential protein stratification in the biomass. Finally, another area of interest in 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

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. The yin-yang driving urinary tract infection and how proteomics can enhance research, diagnostics, and treatment. Floyd KA, Meyer AE, Nelson G, Hadjifrangiskou M (2015) Proteomics Clin Appl 9(11-12): 990-1002
    › Primary publication · 26255866 (PubMed)
  2. Adhesive fiber stratification in uropathogenic Escherichia coli biofilms unveils oxygen-mediated control of type 1 pili. Floyd KA, Moore JL, Eberly AR, Good JA, Shaffer CL, Zaver H, Almqvist F, Skaar EP, Caprioli RM, Hadjifrangiskou M (2015) PLoS Pathog 11(3): e1004697
    › Primary publication · 25738819 (PubMed) · PMC4349694 (PubMed Central)
  3. Dysregulation of Escherichia coli α-hemolysin expression alters the course of acute and persistent urinary tract infection. Nagamatsu K, Hannan TJ, Guest RL, Kostakioti M, Hadjifrangiskou M, Binkley J, Dodson K, Raivio TL, Hultgren SJ (2015) Proc Natl Acad Sci U S A 112(8): E871-80
    › Primary publication · 25675528 (PubMed) · PMC4345586 (PubMed Central)
  4. Pilicide ec240 disrupts virulence circuits in uropathogenic Escherichia coli. Greene SE, Pinkner JS, Chorell E, Dodson KW, Shaffer CL, Conover MS, Livny J, Hadjifrangiskou M, Almqvist F, Hultgren SJ (2014) MBio 5(6): e02038
    › Primary publication · 25352623 (PubMed) · PMC4217179 (PubMed Central)
  5. Strong cross-system interactions drive the activation of the QseB response regulator in the absence of its cognate sensor. Guckes KR, Kostakioti M, Breland EJ, Gu AP, Shaffer CL, Martinez CR, Hultgren SJ, Hadjifrangiskou M (2013) Proc Natl Acad Sci U S A 110(41): 16592-7
    › Primary publication · 24062463 (PubMed) · PMC3799328 (PubMed Central)
  6. Escherichia coli biofilms have an organized and complex extracellular matrix structure. Hung C, Zhou Y, Pinkner JS, Dodson KW, Crowley JR, Heuser J, Chapman MR, Hadjifrangiskou M, Henderson JP, Hultgren SJ (2013) MBio 4(5): e00645-13
    › Primary publication · 24023384 (PubMed) · PMC3774191 (PubMed Central)
  7. Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Kostakioti M, Hadjifrangiskou M, Hultgren SJ (2013) Cold Spring Harb Perspect Med 3(4): a010306
    › Primary publication · 23545571 (PubMed) · PMC3683961 (PubMed Central)
  8. Molecular blueprint of uropathogenic Escherichia coli virulence provides clues toward the development of anti-virulence therapeutics. Kostakioti M, Hultgren SJ, Hadjifrangiskou M (2012) Virulence 3(7): 592-4
    › Primary publication · 23154288 (PubMed) · PMC3545937 (PubMed Central)
  9. Transposon mutagenesis identifies uropathogenic Escherichia coli biofilm factors. Hadjifrangiskou M, Gu AP, Pinkner JS, Kostakioti M, Zhang EW, Greene SE, Hultgren SJ (2012) J Bacteriol 194(22): 6195-205
    › Primary publication · 22984258 (PubMed) · PMC3486386 (PubMed Central)
  10. Distinguishing the contribution of type 1 pili from that of other QseB-misregulated factors when QseC is absent during urinary tract infection. Kostakioti M, Hadjifrangiskou M, Cusumano CK, Hannan TJ, Janetka JW, Hultgren SJ (2012) Infect Immun 80(8): 2826-34
    › Primary publication · 22665375 (PubMed) · PMC3434567 (PubMed Central)
  11. What does it take to stick around? Molecular insights into biofilm formation by uropathogenic Escherichia coli. Hadjifrangiskou M, Hultgren SJ (2012) Virulence 3(3): 231-3
    › Primary publication · 22546905 (PubMed) · PMC3442832 (PubMed Central)
  12. Antitoxins: therapy for stressed bacteria. Hadjifrangiskou M, Kostakioti M, Hultgren SJ (2011) Nat Chem Biol 7(6): 345-7
    › Primary publication · 21587255 (PubMed)
  13. A central metabolic circuit controlled by QseC in pathogenic Escherichia coli. Hadjifrangiskou M, Kostakioti M, Chen SL, Henderson JP, Greene SE, Hultgren SJ (2011) Mol Microbiol 80(6): 1516-29
    › Primary publication · 21542868 (PubMed) · PMC3643513 (PubMed Central)
  14. QseC-mediated dephosphorylation of QseB is required for expression of genes associated with virulence in uropathogenic Escherichia coli. Kostakioti M, Hadjifrangiskou M, Pinkner JS, Hultgren SJ (2009) Mol Microbiol 73(6): 1020-31
    › Primary publication · 19703104 (PubMed) · PMC2963169 (PubMed Central)
  15. Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promoters. Hadjifrangiskou M, Koehler TM (2008) Microbiology 154(Pt 8): 2501-12
    › Primary publication · 18667583 (PubMed) · PMC4225132 (PubMed Central)
  16. The alternative sigma factor sigmaH is required for toxin gene expression by Bacillus anthracis. Hadjifrangiskou M, Chen Y, Koehler TM (2007) J Bacteriol 189(5): 1874-83
    › Primary publication · 17189374 (PubMed) · PMC1855707 (PubMed Central)