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

244 results found

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 coliPathotypes and Principles of Pathogenesis, Editors: Donnenberg, ISBN: 978-0-12-397048-0

Book chapter

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

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

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

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: 2161-2129

Translocation of effector proteins via a type III secretion system (T3SS) is a widespread infection strategy among Gram-negative bacterial pathogens. Each pathogen translocates a particular set of effectors that subvert cell signaling in a way that suits its particular infection cycle. However, as effector unbalance might lead to cytotoxicity, the pathogens must employ mechanisms that regulate the intracellular effector concentration. We present evidence that the effector EspZ controls T3SS effector translocation from enteropathogenic (EPEC) and enterohemorrhagic (EHEC) Escherichia coli. Consistently, an EPEC espZ mutant is highly cytotoxic. Following ectopic expression, we found that EspZ inhibited the formation of actin pedestals as it blocked the translocation of Tir, as well as other effectors, including Map and EspF. Moreover, during infection EspZ inhibited effector translocation following superinfection. Importantly, while EspZ of EHEC O157:H7 had a universal “translocation stop” activity, EspZ of EPEC inhibited effector translocation from typical EPEC strains but not from EHEC O157:H7 or its progenitor, atypical EPEC O55:H7. We found that the N and C termini of EspZ, which contains two transmembrane domains, face the cytosolic leaflet of the plasma membrane at the site of bacterial attachment, while the extracellular loop of EspZ is responsible for its strain-specific activity. These results show that EPEC and EHEC acquired a sophisticated mechanism to regulate the effector translocation.

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

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

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

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: 2161-2129

Rho GTPases are important regulators of many cellular processes. Subversion of Rho GTPases is a common infection strategy employed by many important human pathogens. Enteropathogenic Escherichia coli and enterohemorrhagic Escherichia coli (EPEC and EHEC) translocate the effector EspH, which inactivates mammalian Rho guanine exchange factors (GEFs), as well as Map, EspT, and EspM2, which, by mimicking mammalian RhoGEFs, activate Rho GTPases. In this study we found that EspH induces focal adhesion disassembly, triggers cell detachment, activates caspase-3, and induces cytotoxicity. EspH-induced cell detachment and caspase-3 activation can be offset by EspT, EspM2, and the Salmonella Cdc42/Rac1 GEF effector SopE, which remain active in the presence of EspH. EPEC and EHEC therefore use a novel strategy of controlling Rho GTPase activity by translocating one effector to inactivate mammalian RhoGEFs, replacing them with bacterial RhoGEFs. This study also expands the functional range of bacterial RhoGEFs to include cell adhesion and survival.IMPORTANCE Many human pathogens use a type III secretion system to translocate effectors that can functionally be divided into signaling, disabling, and countervirulence effectors. Among the signaling effectors are those that activate Rho GTPases, which play a central role in coordinating actin dynamics. However, many pathogens also translocate effectors with antagonistic or counteractive functions. For example, Salmonella translocates SopE and SptP, which sequentially turn Rac1 and Cdc42 on and off. In this paper, we show that enteropathogenic E. coli translocates EspH, which inactivates mammalian RhoGEFs and triggers cytotoxicity and at the same time translocates the bacterial RhoGEFs EspM2 and EspT, which are insensitive to EspH, and so neutralizes EspH-induced focal adhesion disassembly, cell detachment, and caspase-3 activation. Our data point to an intriguing infection strategy in which EPEC and EHEC override cellular Rho GTPase

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

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

Clements A, Young JC, Constantinou N, Frankel Get al., 2012, Infection strategies of enteric pathogenic Escherichia coli, GUT MICROBES, Vol: 3, Pages: 71-87, ISSN: 1949-0976

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

Raymond B, Crepin VF, Collins JW, Frankel Get al., 2011, The WxxxE effector EspT triggers expression of immune mediators in an Erk/JNK and NF-kappa B-dependent manner, CELLULAR MICROBIOLOGY, Vol: 13, Pages: 1881-1893, ISSN: 1462-5814

Journal article

Muangman S, Korbsrisate S, Muangsombut V, Srinon V, Adler NL, Schroeder GN, Frankel G, Galyov EEet al., 2011, BopC is a type III secreted effector protein of Burkholderia pseudomallei, FEMS MICROBIOLOGY LETTERS, Vol: 323, Pages: 75-82, ISSN: 0378-1097

Journal article

Shaw RK, Lasa I, Garcia BM, Pallen MJ, Hinton JCD, Berger CN, Frankel Get al., 2011, Cellulose mediates attachment of Salmonella enterica Serovar Typhimurium to tomatoes, ENVIRONMENTAL MICROBIOLOGY REPORTS, Vol: 3, Pages: 569-573, ISSN: 1758-2229

Journal article

Clements A, Smollett K, Lee SF, Hartland EL, Lowe M, Frankel Get al., 2011, EspG of enteropathogenic and enterohemorrhagic E. coli binds the Golgi matrix protein GM130 and disrupts the Golgi structure and function, CELLULAR MICROBIOLOGY, Vol: 13, Pages: 1429-1439, ISSN: 1462-5814

Journal article

Fookes M, Schroeder GN, Langridge GC, Blondel CJ, Mammina C, Connor TR, Seth-Smith H, Vernikos GS, Robinson KS, Sanders M, Petty NK, Kingsley RA, Baeumler AJ, Nuccio S-P, Contreras I, Santiviago CA, Maskell D, Barrow P, Humphrey T, Nastasi A, Roberts M, Frankel G, Parkhill J, Dougan G, Thomson NRet al., 2011, Salmonella bongori Provides Insights into the Evolution of the Salmonellae, PLOS Pathogens, Vol: 7, ISSN: 1553-7366

The genus Salmonella contains two species, S. bongori and S. enterica. Compared to the well-studied S. enterica there is a marked lack of information regarding the genetic makeup and diversity of S. bongori. S. bongori has been found predominantly associated with cold-blooded animals, but it can infect humans. To define the phylogeny of this species, and compare it to S. enterica, we have sequenced 28 isolates representing most of the known diversity of S. bongori. This cross-species analysis allowed us to confidently differentiate ancestral functions from those acquired following speciation, which include both metabolic and virulence-associated capacities. We show that, although S. bongori inherited a basic set of Salmonella common virulence functions, it has subsequently elaborated on this in a different direction to S. enterica. It is an established feature of S. enterica evolution that the acquisition of the type III secretion systems (T3SS-1 and T3SS-2) has been followed by the sequential acquisition of genes encoding secreted targets, termed effectors proteins. We show that this is also true of S. bongori, which has acquired an array of novel effector proteins (sboA-L). All but two of these effectors have no significant S. enterica homologues and instead are highly similar to those found in enteropathogenic Escherichia coli (EPEC). Remarkably, SboH is found to be a chimeric effector protein, encoded by a fusion of the T3SS-1 effector gene sopA and a gene highly similar to the EPEC effector nleH from enteropathogenic E. coli. We demonstrate that representatives of these new effectors are translocated and that SboH, similarly to NleH, blocks intrinsic apoptotic pathways while being targeted to the mitochondria by the SopA part of the fusion. This work suggests that S. bongori has inherited the ancestral Salmonella virulence gene set, but has adapted by incorporating virulence determinants that resemble those employed by EPEC.

Journal article

Wong ARC, Pearson JS, Bright MD, Munera D, Robinson KS, Lee SF, Frankel G, Hartland ELet al., 2011, Enteropathogenic and enterohaemorrhagic Escherichia coli: even more subversive elements, MOLECULAR MICROBIOLOGY, Vol: 80, Pages: 1420-1438, ISSN: 0950-382X

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

Robinson KS, Clements A, Williams AC, Berger CN, Frankel Get al., 2011, Bax Inhibitor 1 in apoptosis and disease, ONCOGENE, Vol: 30, Pages: 2391-2400, ISSN: 0950-9232

Journal article

Pearson JS, Riedmaier P, Marches O, Frankel G, Hartland ELet al., 2011, A type III effector protease NleC from enteropathogenic Escherichia coli targets NF-kappa B for degradation, MOLECULAR MICROBIOLOGY, Vol: 80, Pages: 219-230, ISSN: 0950-382X

Journal article

Petty NK, Feltwell T, Pickard D, Clare S, Toribio AL, Fookes M, Roberts K, Monson R, Nair S, Kingsley RA, Bulgin R, Wiles S, Goulding D, Keane T, Corton C, Lennard N, Harris D, Willey D, Rance R, Yu L, Choudhary JS, Churcher C, Quail MA, Parkhill J, Frankel G, Dougan G, Salmond GPC, Thomson NRet al., 2011, Citrobacter rodentium is an Unstable Pathogen Showing Evidence of Significant Genomic Flux, PLOS PATHOGENS, Vol: 7, ISSN: 1553-7374

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

Shaw RK, Berger CN, Pallen MJ, Sjoeling A, Frankel Get al., 2011, Flagella mediate attachment of enterotoxigenic Escherichia coli to fresh salad leaves, ENVIRONMENTAL MICROBIOLOGY REPORTS, Vol: 3, Pages: 112-117, ISSN: 1758-2229

Journal article

Blanco-Toribio A, Muyldermans S, Frankel G, Angel Fernandez Let al., 2010, Direct Injection of Functional Single-Domain Antibodies from E. coli into Human Cells, PLOS ONE, Vol: 5, ISSN: 1932-6203

Journal article

Martinez E, Schroeder GN, Berger CN, Lee SF, Robinson KS, Badea L, Simpson N, Hall RA, Hartland EL, Crepin VF, Frankel Get al., 2010, Binding to Na+/H+ exchanger regulatory factor 2 (NHERF2) affects trafficking and function of the enteropathogenic Escherichia coli type III secretion system effectors Map, EspI and NleH, CELLULAR MICROBIOLOGY, Vol: 12, Pages: 1718-1731, ISSN: 1462-5814

Journal article

Schroeder GN, Petty NK, Mousnier A, Harding CR, Vogrin AJ, Wee B, Fry NK, Harrison TG, Newton HJ, Thomson NR, Beatson SA, Dougan G, Hartland EL, Frankel Get al., 2010, Legionella pneumophila Strain 130b Possesses a Unique Combination of Type IV Secretion Systems and Novel Dot/Icm Secretion System Effector Proteins, JOURNAL OF BACTERIOLOGY, Vol: 192, Pages: 6001-6016, ISSN: 0021-9193

Journal article

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