Imperial College London

ProfessorGadFrankel

Faculty of Natural SciencesDepartment of Life Sciences

Professor of Molecular Pathogenesis
 
 
 
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Contact

 

+44 (0)20 7594 5253g.frankel

 
 
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Location

 

1.46Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

227 results found

Baumann D, Salia H, Greune L, Norkowski S, Körner B, Uckeley ZM, Frankel G, Guenot M, Rüter C, Schmidt MAet al., 2018, Multitalented EspB of enteropathogenic Escherichia coli (EPEC) enters cells autonomously and induces programmed cell death in human monocytic THP-1 cells., Int J Med Microbiol, Vol: 308, Pages: 387-404

Enteropathogenic Escherichia coli (EPEC) subvert host cell signaling pathways by injecting effector proteins via a Type 3 Secretion System (T3SS). The T3SS-dependent EspB protein is a multi-functional effector protein, which contributes to adherence and translocator pore formation and after injection exhibits several intracellular activities. In addition, EspB is also secreted into the environment. Effects of secreted EspB have not been reported thus far. As a surrogate for secreted EspB we employed recombinant EspB (rEspB) derived from the prototype EPEC strain E2348/69 and investigated the interactions of the purified protein with different human epithelial and immune cells including monocytic THP-1 cells, macrophages, dendritic cells, U-937, epithelial T84, Caco-2, and HeLa cells. To assess whether these proteins might exert a cytotoxic effect we monitored the release of lactate dehydrogenase (LDH) as well as propidium iodide (PI) uptake. For comparison, we also investigated several homologs of EspB such as IpaD of Shigella, and SipC, SipD, SseB, and SseD of Salmonella as purified recombinant proteins. Interestingly, cytotoxicity was only observed in THP-1 cells and macrophages, whereas epithelial cells remained unaffected. Cell fractionation and immune fluorescence experiments showed that rEspB enters cells autonomously, which suggests that EspB might qualify as a novel cell-penetrating effector protein (CPE). Using specific organelle tracers and inhibitors of signaling pathways we found that rEspB destroys the mitochondrial membrane potential - an indication of programmed cell death induction in THP-1 cells. Here we show that EspB not only constitutes an essential part of the T3SS-nanomachine and contributes to the arsenal of injected effector proteins but, furthermore, that secreted (recombinant) EspB autonomously enters host cells and selectively induces cell death in immune cells.

JOURNAL ARTICLE

Johnson R, Ravenhall M, Pickard D, Dougan G, Byrne A, Frankel Get al., 2018, Comparison of Salmonella enterica Serovars Typhi and Typhimurium Reveals Typhoidal Serovar-Specific Responses to Bile, INFECTION AND IMMUNITY, Vol: 86, ISSN: 0019-9567

JOURNAL ARTICLE

Mullineaux-Sanders C, Suez J, Elinav E, Frankel Get al., 2018, Sieving through gut models of colonization resistance, NATURE MICROBIOLOGY, Vol: 3, Pages: 132-140, ISSN: 2058-5276

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Pollard DJ, Berger CN, So EC, Yu L, Hadavizadeh K, Jennings P, Tate EW, Choudhary JS, Frankel Get al., 2018, Broad-Spectrum Regulation of Nonreceptor Tyrosine Kinases by the Bacterial ADP-Ribosyltransferase EspJ, MBIO, Vol: 9, ISSN: 2150-7511

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Ale A, Crepin VF, Collins JW, Constantinou N, Habibzay M, Babtie AC, Frankel G, Stumpf MPHet al., 2017, Model of Host-Pathogen Interaction Dynamics Links In Vivo Optical Imaging and Immune Responses, INFECTION AND IMMUNITY, Vol: 85, ISSN: 0019-9567

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Berger CN, Crepin VF, Roumeliotis TI, Wright JC, Carson D, Pevsner-Fischer M, Furniss RCD, Dougan G, Dori-Bachash M, Yu L, Clements A, Collins JW, Elinav E, Larrouy-Maumus GJ, Choudhary JS, Frankel Get al., 2017, Citrobacter rodentium Subverts ATP Flux and Cholesterol Homeostasis in Intestinal Epithelial Cells In Vivo, CELL METABOLISM, Vol: 26, Pages: 738-+, ISSN: 1550-4131

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Cepeda-Molero M, Berger CN, Walsham ADS, Ellis SJ, Wemyss-Holden S, Schueller S, Frankel G, Angel Fernandez Let al., 2017, Attaching and effacing (A/E) lesion formation by enteropathogenic E. coli on human intestinal mucosa is dependent on non-LEE effectors, PLOS PATHOGENS, Vol: 13, ISSN: 1553-7366

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Johnson R, Byrne A, Berger CN, Klemm E, Crepin VF, Dougan G, Frankel Get al., 2017, The Type III Secretion System Effector SptP of Salmonella enterica Serovar Typhi, JOURNAL OF BACTERIOLOGY, Vol: 199, ISSN: 0021-9193

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Mullineaux-Sanders C, Collins JW, Ruano-Gallego D, Levy M, Pevsner-Fischer M, Glegola-Madejska IT, Sagfors AM, Wong JLC, Elinav E, Crepin VF, Frankel Get al., 2017, Citrobacter rodentium Relies on Commensals for Colonization of the Colonic Mucosa, CELL REPORTS, Vol: 21, Pages: 3381-3389, ISSN: 2211-1247

JOURNAL ARTICLE

Pallett MA, Crepin VF, Serafini N, Habibzay M, Kotik O, Sanchez-Garrido J, Di Santo JP, Shenoy AR, Berger CN, Frankel Get al., 2017, Bacterial virulence factor inhibits caspase-4/11 activation in intestinal epithelial cells, MUCOSAL IMMUNOLOGY, Vol: 10, Pages: 602-612, ISSN: 1933-0219

JOURNAL ARTICLE

Pearson JS, Giogha C, Muhlen S, Nachbur U, Pham CLL, Zhang Y, Hildebrand JM, Oates CV, Lung TWF, Ingle D, Dagley LF, Bankovacki A, Petrie EJ, Schroeder GN, Crepin VF, Frankel G, Masters SL, Vince J, Murphy JM, Sunde M, Webb AI, Silke J, Hartland ELet al., 2017, EspL is a bacterial cysteine protease effector that cleaves RHIM proteins to block necroptosis and inflammation, NATURE MICROBIOLOGY, Vol: 2, ISSN: 2058-5276

JOURNAL ARTICLE

Portaliou AG, Tsolis KC, Loos MS, Balabanidou V, Rayo J, Tsirigotaki A, Crepin VF, Frankel G, Kalodimos CG, Karamanou S, Economou Aet al., 2017, Hierarchical protein targeting and secretion is controlled by an affinity switch in the type III secretion system of enteropathogenic Escherichia coli, EMBO JOURNAL, Vol: 36, Pages: 3517-3531, ISSN: 0261-4189

JOURNAL ARTICLE

Sandu P, Crepin VF, Drechsler H, McAinsh AD, Frankel G, Berger CNet al., 2017, The Enterohemorrhagic Escherichia coli Effector EspW Triggers Actin Remodeling in a Rac1-Dependent Manner, INFECTION AND IMMUNITY, Vol: 85, ISSN: 0019-9567

JOURNAL ARTICLE

Witcomb LA, Czupryna J, Francis KP, Frankel G, Taylor PWet al., 2017, Non-invasive three-dimensional imaging of Escherichia coli K1 infection using diffuse light imaging tomography combined with micro-computed tomography, METHODS, Vol: 127, Pages: 62-68, ISSN: 1046-2023

JOURNAL ARTICLE

Crepin VF, Collins JW, Habibzay M, Frankel Get al., 2016, Citrobacter rodentium mouse model of bacterial infection., Nat Protoc, Vol: 11, Pages: 1851-1876

Infection of mice with Citrobacter rodentium is a robust model to study bacterial pathogenesis, mucosal immunology, the health benefits of probiotics and the role of the microbiota during infection. C. rodentium was first isolated by Barthold from an outbreak of mouse diarrhea in Yale University in 1972 and was 'rediscovered' by Falkow and Schauer in 1993. Since then the use of the model has proliferated, and it is now the gold standard for studying virulence of the closely related human pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). Here we provide a detailed protocol for various applications of the model, including bacterial growth, site-directed mutagenesis, mouse inoculation (from cultured cells and after cohabitation), monitoring of bacterial colonization, tissue extraction and analysis, immune responses, probiotic treatment and microbiota analysis. The main protocol, from mouse infection to clearance and analysis of tissues and host responses, takes ∼5 weeks to complete.

JOURNAL ARTICLE

Furniss RCD, Slater S, Frankel G, Clements Aet al., 2016, Enterohaemorrhagic E. coli modulates an ARF6:Rab35 signaling axis to prevent recycling endosome maturation during infection, JOURNAL OF MOLECULAR BIOLOGY, Vol: 428, Pages: 3399-3407, ISSN: 0022-2836

JOURNAL ARTICLE

Pollard DJ, Young JC, Covarelli V, Herrera-Leon S, Connor TR, Fookes M, Walker D, Echeita A, Thomson NR, Berger CN, Frankel Get al., 2016, The Type III Secretion System Effector SeoC of Salmonella enterica subsp salamae and S. enterica subsp arizonae ADP-Ribosylates Src and Inhibits Opsonophagocytosis, INFECTION AND IMMUNITY, Vol: 84, Pages: 3618-3628, ISSN: 0019-9567

JOURNAL ARTICLE

So EC, Schroeder GN, Carson D, Mattheis C, Mousnier A, Broncel M, Tate EW, Frankel Get al., 2016, The Rab-binding Profiles of Bacterial Virulence Factors during Infection, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 291, Pages: 5832-5843, ISSN: 0021-9258

JOURNAL ARTICLE

Crepin VF, Habibzay M, Glegola-Madejska I, Guenot M, Collins JW, Frankel Get al., 2015, Tir Triggers Expression of CXCL1 in Enterocytes and Neutrophil Recruitment during Citrobacter rodentium Infection, INFECTION AND IMMUNITY, Vol: 83, Pages: 3342-3354, ISSN: 0019-9567

JOURNAL ARTICLE

Hunter PJ, Shaw RK, Berger CN, Frankel G, Pink D, Hand Pet al., 2015, Older leaves of lettuce (Lactuca spp.) support higher levels of Salmonella enterica ser. Senftenberg attachment and show greater variation between plant accessions than do younger leaves, FEMS MICROBIOLOGY LETTERS, Vol: 362, ISSN: 0378-1097

JOURNAL ARTICLE

Messens W, Bolton D, Frankel G, Liebana E, McLauchlin J, Morabito S, Oswald E, Threlfall EJet al., 2015, Defining pathogenic verocytotoxin-producing Escherichia coli (VTEC) from cases of human infection in the European Union, 2007-2010, EPIDEMIOLOGY AND INFECTION, Vol: 143, Pages: 1652-1661, ISSN: 0950-2688

JOURNAL ARTICLE

Schreiber F, Kay S, Frankel G, Clare S, Goulding D, van de Vosse E, van Dissel JT, Strugnell R, Thwaites G, Kingsley RA, Dougan G, Baker Set al., 2015, The Hd, Hj, and Hz66 flagella variants of Salmonella enterica serovar Typhi modify host responses and cellular interactions, SCIENTIFIC REPORTS, Vol: 5, ISSN: 2045-2322

JOURNAL ARTICLE

Schroeder GN, Aurass P, Oates CV, Tate EW, Hartland EL, Flieger A, Frankel Get al., 2015, Legionella pneumophila Effector LpdA Is a Palmitoylated Phospholipase D Virulence Factor, INFECTION AND IMMUNITY, Vol: 83, Pages: 3989-4002, ISSN: 0019-9567

JOURNAL ARTICLE

So EC, Mattheis C, Tate EW, Frankel G, Schroeder GNet al., 2015, Creating a customized intracellular niche: subversion of host cell signaling by Legionella type IV secretion system effectors, CANADIAN JOURNAL OF MICROBIOLOGY, Vol: 61, Pages: 617-635, ISSN: 0008-4166

JOURNAL ARTICLE

Witcomb LA, Collins JW, McCarthy AJ, Frankel G, Taylor PWet al., 2015, Bioluminescent Imaging Reveals Novel Patterns of Colonization and Invasion in Systemic Escherichia coli K1 Experimental Infection in the Neonatal Rat, INFECTION AND IMMUNITY, Vol: 83, Pages: 4528-4540, ISSN: 0019-9567

JOURNAL ARTICLE

Clements A, Stoneham CA, Furniss RCD, Frankel Get al., 2014, Enterohaemorrhagic Escherichia coli inhibits recycling endosome function and trafficking of surface receptors, CELLULAR MICROBIOLOGY, Vol: 16, Pages: 1693-1705, ISSN: 1462-5814

JOURNAL ARTICLE

Collins JW, Chervaux C, Raymond B, Derrien M, Brazeilles R, Kosta A, Chambaud I, Crepin VF, Frankel Get al., 2014, Fermented Dairy Products Modulate Citrobacter rodentium-Induced Colonic Hyperplasia, JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: 1029-1041, ISSN: 0022-1899

JOURNAL ARTICLE

Collins JW, Keeney KM, Crepin VE, Rathinam VAK, Fitzgerald KA, Finlay BB, Frankel Get al., 2014, Citrobacter rodentium: infection, inflammation and the microbiota, NATURE REVIEWS MICROBIOLOGY, Vol: 12, Pages: 612-623, ISSN: 1740-1526

JOURNAL ARTICLE

Mousnier A, Schroeder GN, Stoneham CA, So EC, Garnett JA, Yu L, Matthews SJ, Choudhary JS, Hartland EL, Frankel Get al., 2014, A New Method To Determine In Vivo Interactomes Reveals Binding of the Legionella pneumophila Effector PieE to Multiple Rab GTPases, MBIO, Vol: 5, ISSN: 2150-7511

JOURNAL ARTICLE

Pallett MA, Berger CN, Pearson JS, Hartland EL, Frankel Get al., 2014, The Type III Secretion Effector NleF of Enteropathogenic Escherichia coli Activates NF-kappa B Early during Infection, INFECTION AND IMMUNITY, Vol: 82, Pages: 4878-4888, ISSN: 0019-9567

JOURNAL ARTICLE

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