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

Satoh-Takayama N, Serafini N, Verrier T, Rekiki A, Renauld J-C, Frankel G, Di Santo JPet al., 2014, The Chemokine Receptor CXCR6 Controls the Functional Topography of Interleukin-22 Producing Intestinal Innate Lymphoid Cells, IMMUNITY, Vol: 41, Pages: 776-788, ISSN: 1074-7613

JOURNAL ARTICLE

Song-Zhao GX, Srinivasan N, Pott J, Baban D, Frankel G, Maloy KJet al., 2014, Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen, MUCOSAL IMMUNOLOGY, Vol: 7, Pages: 763-774, ISSN: 1933-0219

JOURNAL ARTICLE

Stevens MP, Frankel GM, 2014, The Locus of Enterocyte Effacement and Associated Virulence Factors of Enterohemorrhagic Escherichia coli., Microbiol Spectr, Vol: 2

A subset of Shiga toxin-producing Escherichia coli strains, termed enterohemorrhagic E. coli (EHEC), is defined in part by the ability to produce attaching and effacing (A/E) lesions on intestinal epithelia. Such lesions are characterized by intimate bacterial attachment to the apical surface of enterocytes, cytoskeletal rearrangements beneath adherent bacteria, and destruction of proximal microvilli. A/E lesion formation requires the locus of enterocyte effacement (LEE), which encodes a Type III secretion system that injects bacterial proteins into host cells. The translocated proteins, termed effectors, subvert a plethora of cellular pathways to the benefit of the pathogen, for example, by recruiting cytoskeletal proteins, disrupting epithelial barrier integrity, and interfering with the induction of inflammation, phagocytosis, and apoptosis. The LEE and selected effectors play pivotal roles in intestinal persistence and virulence of EHEC, and it is becoming clear that effectors may act in redundant, synergistic, and antagonistic ways during infection. Vaccines that target the function of the Type III secretion system limit colonization of reservoir hosts by EHEC and may thus aid control of zoonotic infections. Here we review the features and functions of the LEE-encoded Type III secretion system and associated effectors of E. coli O157:H7 and other Shiga toxin-producing E. coli strains.

JOURNAL ARTICLE

Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang J-P, Brown EM, Frankel G, Levy M, Katz MN, Philbrick WM, Elinav E, Finlay BB, Flavell RAet al., 2014, NLRP6 Inflammasome Orchestrates the Colonic Host-Microbial Interface by Regulating Goblet Cell Mucus Secretion, CELL, Vol: 156, Pages: 1045-1059, ISSN: 0092-8674

JOURNAL ARTICLE

Young JC, Clements A, Lang AE, Garnett JA, Munera D, Arbeloa A, Pearson J, Hartland EL, Matthews SJ, Mousnier A, Barry DJ, Way M, Schlosser A, Aktories K, Frankel Get al., 2014, The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723

JOURNAL ARTICLE

Aurass P, Schlegel M, Metwally O, Harding CR, Schroeder GN, Frankel G, Flieger Aet al., 2013, The Legionella pneumophila Dot/Icm-secreted Effector PlcC/CegC1 Together with PlcA and PlcB Promotes Virulence and Belongs to a Novel Zinc Metallophospholipase C Family Present in Bacteria and Fungi, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 288, Pages: 11080-11092, ISSN: 0021-9258

JOURNAL ARTICLE

Clare S, John V, Walker AW, Hill JL, Abreu-Goodger C, Hale C, Goulding D, Lawley TD, Mastroeni P, Frankel G, Enright AJ, Vigorito E, Dougan Get al., 2013, Enhanced Susceptibility to Citrobacter rodentium Infection in MicroRNA-155-Deficient Mice, INFECTION AND IMMUNITY, Vol: 81, Pages: 723-732, ISSN: 0019-9567

JOURNAL ARTICLE

Clements A, Berger CN, Lomma M, Frankel Get al., 2013, Type 3 secretion effectors, Escherichia coli: Pathotypes and Principles of Pathogenesis: Second Edition, Pages: 451-497, ISBN: 9780123970480

© 2015 Elsevier Inc. All rights reserved. Enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), and Shigella use a type 3 secretion system (T3SS) to inject dozens of effector proteins into the host cell. The effectors manipulate host cell processes including the host cytoskeleton, immune response, cell survival, and gut integrity. EPEC and EHEC share a large number of common effectors and some homologous effectors can be found in Shigella, however there is also considerable variability within and between pathotypes. For many effectors detailed molecular mechanisms of action have been described by identifying host interacting partners, homologous proteins, or enzymatic activities. However, understanding effector biology within the context of infection with multiple effectors, various cell populations, and host genetic differences remains a challenge.

BOOK CHAPTER

Collins JW, Meganck JA, Kuo C, Francis KP, Frankel Get al., 2013, 4D Multimodality Imaging of Citrobacter rodentium Infections in Mice, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X

JOURNAL ARTICLE

Harding CR, Mattheis C, Mousnier A, Oates CV, Hartland EL, Frankel G, Schroeder GNet al., 2013, LtpD Is a Novel Legionella pneumophila Effector That Binds Phosphatidylinositol 3-Phosphate and Inositol Monophosphatase IMPA1, INFECTION AND IMMUNITY, Vol: 81, Pages: 4261-4270, ISSN: 0019-9567

JOURNAL ARTICLE

Harding CR, Schroeder GN, Collins JW, Frankel Get al., 2013, Use of Galleria mellonella as a Model Organism to Study Legionella pneumophila Infection, JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, ISSN: 1940-087X

JOURNAL ARTICLE

Harding CR, Stoneham CA, Schuelein R, Newton H, Oates CV, Hartland EL, Schroeder GN, Frankel Get al., 2013, The Dot/Icm Effector SdhA Is Necessary for Virulence of Legionella pneumophila in Galleria mellonella and A/J Mice, INFECTION AND IMMUNITY, Vol: 81, Pages: 2598-2605, ISSN: 0019-9567

JOURNAL ARTICLE

Lai Y, Rosenshine I, Leong JM, Frankel Get al., 2013, Intimate host attachment: enteropathogenic and enterohaemorrhagic Escherichia coli, CELLULAR MICROBIOLOGY, Vol: 15, Pages: 1796-1808, ISSN: 1462-5814

JOURNAL ARTICLE

Pearson JS, Giogha C, Ong SY, Kennedy CL, Kelly M, Robinson KS, Lung TWF, Mansell A, Riedmaier P, Oates CVL, Zaid A, Muehlen S, Crepin VF, Marches O, Ang C-S, Williamson NA, O'Reilly LA, Bankovacki A, Nachbur U, Infusini G, Webb AI, Silke J, Strasser A, Frankel G, Hartland ELet al., 2013, A type III effector antagonizes death receptor signalling during bacterial gut infection, NATURE, Vol: 501, Pages: 247-+, ISSN: 0028-0836

JOURNAL ARTICLE

Raymond B, Young JC, Pallett M, Endres RG, Clements A, Frankel Get al., 2013, Subversion of trafficking, apoptosis, and innate immunity by type III secretion system effectors, TRENDS IN MICROBIOLOGY, Vol: 21, Pages: 430-439, ISSN: 0966-842X

JOURNAL ARTICLE

Vogrin AJ, Mousnier A, Frankel G, Hartland ELet al., 2013, Subcellular localization of legionella Dot/Icm effectors., Methods Mol Biol, Vol: 954, Pages: 333-344

The translocation of effector proteins by the Dot/Icm type IV secretion system is central to the ability of Legionella pneumophila to persist and replicate within eukaryotic cells. The subcellular localization of translocated Dot/Icm proteins in host cells provides insight into their function. Through co-staining with host cell markers, effector proteins may be localized to specific subcellular compartments and membranes, which frequently reflects their host cell target and mechanism of action. In this chapter, we describe protocols to (1) localize effector proteins within cells by ectopic expression using green fluorescent protein fusions and (2) localize effector proteins within infected cells using epitope-tagged effector proteins and immuno-fluorescence microscopy.

JOURNAL ARTICLE

Berger CN, Crepin VF, Baruch K, Mousnier A, Rosenshine I, Frankel Get al., 2012, EspZ of Enteropathogenic and Enterohemorrhagic Escherichia coli Regulates Type III Secretion System Protein Translocation, MBIO, Vol: 3, ISSN: 2150-7511

JOURNAL ARTICLE

Clements A, Young JC, Constantinou N, Frankel Get al., 2012, Infection strategies of enteric pathogenic Escherichia coli., Gut Microbes, Vol: 3, Pages: 71-87

Enteric Escherichia coli (E. coli) are both natural flora of humans and important pathogens causing significant morbidity and mortality worldwide. Traditionally enteric E. coli have been divided into 6 pathotypes, with further pathotypes often proposed. In this review we suggest expansion of the enteric E. coli into 8 pathotypes to include the emerging pathotypes of adherent invasive E. coli (AIEC) and Shiga-toxin producing enteroaggregative E. coli (STEAEC). The molecular mechanisms that allow enteric E. coli to colonize and cause disease in the human host are examined and for two of the pathotypes that express a type 3 secretion system (T3SS) we discuss the complex interplay between translocated effectors and manipulation of host cell signaling pathways that occurs during infection.

JOURNAL ARTICLE

Collins JW, Akin AR, Kosta A, Zhang N, Tangney M, Francis KP, Frankel Get al., 2012, Pre-treatment with Bifidobacterium breve UCC2003 modulates Citrobacter rodentium-induced colonic inflammation and organ specificity, MICROBIOLOGY-SGM, Vol: 158, Pages: 2826-2834, ISSN: 1350-0872

JOURNAL ARTICLE

Dart AE, Tollis S, Bright MD, Frankel G, Endres RGet al., 2012, The motor protein myosin 1G functions in Fc gamma R-mediated phagocytosis, JOURNAL OF CELL SCIENCE, Vol: 125, Pages: 6020-6029, ISSN: 0021-9533

JOURNAL ARTICLE

Dolezal P, Aili M, Tong J, Jiang J-H, Marobbio CM, Lee SF, Schuelein R, Belluzzo S, Binova E, Mousnier A, Frankel G, Giannuzzi G, Palmieri F, Gabriel K, Naderer T, Hartland EL, Lithgow Tet al., 2012, Legionella pneumophila Secretes a Mitochondrial Carrier Protein during Infection, PLOS PATHOGENS, Vol: 8, ISSN: 1553-7366

JOURNAL ARTICLE

Harding CR, Schroeder GN, Reynolds S, Kosta A, Collins JW, Mousnier A, Frankel Get al., 2012, Legionella pneumophila Pathogenesis in the Galleria mellonella Infection Model, INFECTION AND IMMUNITY, Vol: 80, Pages: 2780-2790, ISSN: 0019-9567

JOURNAL ARTICLE

Islam MS, Shaw RK, Frankel G, Pallen MJ, Busby SJWet al., 2012, Translation of a minigene in the 5 ' leader sequence of the enterohaemorrhagic Escherichia coli LEE1 transcription unit affects expression of the neighbouring downstream gene, BIOCHEMICAL JOURNAL, Vol: 441, Pages: 247-253, ISSN: 0264-6021

JOURNAL ARTICLE

Munera D, Martinez E, Varyukhina S, Mahajan A, Ayala-Sanmartin J, Frankel Get al., 2012, Recruitment and membrane interactions of host cell proteins during attachment of enteropathogenic and enterohaemorrhagic Escherichia coli, BIOCHEMICAL JOURNAL, Vol: 445, Pages: 383-392, ISSN: 0264-6021

JOURNAL ARTICLE

Nesta B, Spraggon G, Alteri C, Moriel DG, Rosini R, Veggi D, Smith S, Bertoldi I, Pastorello I, Ferlenghi I, Fontana MR, Frankel G, Mobley HLT, Rappuoli R, Pizza M, Serino L, Soriani Met al., 2012, FdeC, a Novel Broadly Conserved Escherichia coli Adhesin Eliciting Protection against Urinary Tract Infections, MBIO, Vol: 3, ISSN: 2150-7511

JOURNAL ARTICLE

Wong ARC, Clements A, Raymond B, Crepin VF, Frankel Get al., 2012, The Interplay between the Escherichia coli Rho Guanine Nucleotide Exchange Factor Effectors and the Mammalian RhoGEF Inhibitor EspH, MBIO, Vol: 3, ISSN: 2150-7511

JOURNAL ARTICLE

Wong ARC, Raymond B, Collins JW, Crepin VF, Frankel Get al., 2012, The enteropathogenic E. coli effector EspH promotes actin pedestal formation and elongation via WASP-interacting protein (WIP), CELLULAR MICROBIOLOGY, Vol: 14, Pages: 1051-1070, ISSN: 1462-5814

JOURNAL ARTICLE

Arbeloa A, Oates CV, Marches O, Hartland EL, Frankel Get al., 2011, Enteropathogenic and Enterohemorrhagic Escherichia coli Type III Secretion Effector EspV Induces Radical Morphological Changes in Eukaryotic Cells, INFECTION AND IMMUNITY, Vol: 79, Pages: 1067-1076, ISSN: 0019-9567

JOURNAL ARTICLE

Berger CN, Brown DJ, Shaw RK, Minuzzi F, Feys B, Frankel Get al., 2011, Salmonella enterica strains belonging to O serogroup 1,3,19 induce chlorosis and wilting of Arabidopsis thaliana leaves, ENVIRONMENTAL MICROBIOLOGY, Vol: 13, Pages: 1299-1308, ISSN: 1462-2912

JOURNAL ARTICLE

Bright MD, Frankel G, 2011, PAK4 phosphorylates myosin regulatory light chain and contributes to Fc gamma receptor-mediated phagocytosis, INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, Vol: 43, Pages: 1776-1781, ISSN: 1357-2725

JOURNAL ARTICLE

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