Imperial College London

ProfessorDavidHolden

Faculty of MedicineDepartment of Medicine

Professor
 
 
 
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Contact

 

+44 (0)20 7594 3073d.holden

 
 
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Location

 

221Flowers buildingSouth Kensington Campus

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Summary

 

Publications

Publication Type
Year
to

121 results found

Godlee C, Cerny O, Durkin CH, Holden DWet al., 2019, SrcA is a chaperone for the Salmonella SPI-2 type three secretion system effector SteD., Microbiology, Vol: 165, Pages: 15-25

Effector proteins of type three secretion systems (T3SS) often require cytosolic chaperones for their stabilization, to interact with the secretion machinery and to enable effector delivery into host cells. We found that deletion of srcA, previously shown to encode a chaperone for the Salmonella pathogenicity island 2 (SPI-2) T3SS effectors SseL and PipB2, prevented the reduction of mature Major Histocompatibility Complex class II (mMHCII) from the surface of antigen-presenting cells during Salmonella infection. This activity was shown previously to be caused by the SPI-2 T3SS effector SteD. Since srcA and steD are located in the same operon on the Salmonella chromosome, this suggested that the srcA phenotype might be due to an indirect effect on SteD. We found that SrcA is not translocated by the SPI-2 T3SS but interacts directly and forms a stable complex with SteD in bacteria with a 2 : 1 stoichiometry. We found that SrcA was not required for SPI-2 T3SS-dependent, neutral pH-induced secretion of either SseL or PipB2 but was essential for secretion of SteD. SrcA therefore functions as a chaperone for SteD, explaining its requirement for the reduction in surface levels of mMHCII.

JOURNAL ARTICLE

Holden DW, Errington J, 2018, Type II Toxin-Antitoxin Systems and Persister Cells, MBIO, Vol: 9, ISSN: 2150-7511

JOURNAL ARTICLE

Jennings E, Thurston TLM, Holden DW, 2017, Salmonella SPI-2 Type III Secretion System Effectors: Molecular Mechanisms And Physiological Consequences, CELL HOST & MICROBE, Vol: 22, Pages: 217-231, ISSN: 1931-3128

JOURNAL ARTICLE

Gunster RA, Matthews SA, Holden DW, Thurston TLMet al., 2017, SseK1 and SseK3 Type III Secretion System Effectors Inhibit NF-kappa B Signaling and Necroptotic Cell Death in Salmonella-Infected Macrophages, INFECTION AND IMMUNITY, Vol: 85, ISSN: 0019-9567

JOURNAL ARTICLE

Grabe GJ, Zhang Y, Przydacz M, Rolhion N, Yang Y, Pruneda JN, Komander D, Holden DW, Hare SAet al., 2016, The Salmonella Effector SpvD Is a Cysteine Hydrolase with a Serovar-specific Polymorphism Influencing Catalytic Activity, Suppression of Immune Responses, and Bacterial Virulence, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 291, Pages: 25853-25863, ISSN: 0021-9258

JOURNAL ARTICLE

Thurston TLM, Matthews SA, Jennings E, Alix E, Shao F, Shenoy AR, Birrell MA, Holden DWet al., 2016, Growth inhibition of cytosolic Salmonella by caspase-1 and caspase-11 precedes host cell death, NATURE COMMUNICATIONS, Vol: 7, ISSN: 2041-1723

JOURNAL ARTICLE

Pruneda JN, Durkin CH, Geurink PP, Ovaa H, Santhanam B, Holden DW, Komander Det al., 2016, The Molecular Basis for Ubiquitin and Ubiquitin-like Specificities in Bacterial Effector Proteases, MOLECULAR CELL, Vol: 63, Pages: 261-276, ISSN: 1097-2765

JOURNAL ARTICLE

Santos AJM, Durkin CH, Helaine S, Boucrot E, Holden DWet al., 2016, Clustered Intracellular Salmonella enterica Serovar Typhimurium Blocks Host Cell Cytokinesis, INFECTION AND IMMUNITY, Vol: 84, Pages: 2149-2158, ISSN: 0019-9567

JOURNAL ARTICLE

Domingues L, Ismail A, Charro N, Rodriguez-Escudero I, Holden DW, Molina M, Cid VJ, Mota LJet al., 2016, The Salmonella effector SteA binds phosphatidylinositol 4-phosphate for subcellular targeting within host cells, CELLULAR MICROBIOLOGY, Vol: 18, Pages: 949-969, ISSN: 1462-5814

JOURNAL ARTICLE

Mouton JM, Helaine S, Holden DW, Sampson SLet al., 2016, Elucidating population-wide mycobacterial replication dynamics at the single-cell level, MICROBIOLOGY-SGM, Vol: 162, Pages: 966-978, ISSN: 1350-0872

JOURNAL ARTICLE

O'Neill AM, Thurston TLM, Holden DW, 2016, Cytosolic Replication of Group A Streptococcus in Human Macrophages (vol 7, e00020-16, 2016), MBIO, Vol: 7, ISSN: 2150-7511

JOURNAL ARTICLE

Rolhion N, Furniss RCD, Grabe G, Ryan A, Liu M, Matthews SA, Holden DWet al., 2016, Inhibition of Nuclear Transport of NF-kappa B p65 by the Salmonella Type III Secretion System Effector SpvD, PLOS PATHOGENS, Vol: 12, ISSN: 1553-7366

JOURNAL ARTICLE

Pratap CB, Scanu T, Spaapen RM, Bakker JM, Wu L-E, Hofland I, Broeks A, Shukla VK, Kumar M, Janssen H, Song J-Y, Riele HT, Holden DW, Nath G, Neefjes Jet al., 2016, Salmonella manipulation of host signalling pathways promotes cellular transformation and cancer of infected tissues, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 45, Pages: 145-145, ISSN: 1201-9712

JOURNAL ARTICLE

O'Neill AM, Thurston TLM, Holden DW, 2016, Cytosolic Replication of Group A Streptococcus in Human Macrophages, MBIO, Vol: 7, ISSN: 2150-7511

JOURNAL ARTICLE

Scanu T, Spaapen RM, Bakker JM, Pratap CB, Wu L-E, Hofland I, Broeks A, Shukla VK, Kumar M, Janssen H, Song J-Y, Neefjes-Borst EA, te Riele H, Holden DW, Nath G, Neefjes Jet al., 2015, Salmonella Manipulation of Host Signaling Pathways Provokes Cellular Transformation Associated with Gallbladder Carcinoma, CELL HOST & MICROBE, Vol: 17, Pages: 763-774, ISSN: 1931-3128

JOURNAL ARTICLE

Almeida MT, Mesquita FS, Cruz R, Osorio H, Custodio R, Brito C, Vingadassalom D, Martins M, Leong JM, Holden DW, Cabanes D, Sousa Set al., 2015, Src-dependent Tyrosine Phosphorylation of Non-muscle Myosin Heavy Chain-IIA Restricts Listeria monocytogenes Cellular Infection, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 290, Pages: 8383-8395, ISSN: 0021-9258

JOURNAL ARTICLE

, 2015, Interactions between Salmonella and the Autophagy System, Autophagy, Infection, and the Immune Response, Pages: 201-217, ISBN: 9781118677551

© 2015 by John Wiley & Sons, Inc. All rights reserved. The uptake of bacteria by host cells results in the formation of a membrane-bound vacuole that is usually processed into a degradative phagolysosome. However, in some cases the vacuolar membrane can rupture, releasing bacteria into the host cell cytosol. In addition to its role in degrading cellular constituents in response to cell stress, autophagy is a form of innate immunity that helps to maintain the sterility of the cytosol. This chapter will focus on the interaction of the bacterial pathogen Salmonella enterica with the autophagy system. We discuss how autophagy can restrict Salmonella replication. However, as co-evolution of host and bacterium can result in pathogenic bacteria acquiring immune avoidance proteins, we also discuss the possibility of evasion of antibacterial autophagy by Salmonella.

BOOK CHAPTER

Holden DW, Philpott DJ, 2015, Editorial overview: Host-microbe interactions: bacteria, CURRENT OPINION IN MICROBIOLOGY, Vol: 23, Pages: V-VIII, ISSN: 1369-5274

JOURNAL ARTICLE

McEwan DG, Richter B, Claudi B, Wigge C, Wild P, Farhan H, McGourty K, Coxon FP, Franz-Wachtel M, Perdu B, Akutsu M, Habermann A, Kirchof A, Helfrich MH, Odgren PR, Van Hul W, Frangakis AS, Rajalingam K, Macek B, Holden DW, Bumann D, Dikic Iet al., 2015, PLEKHM1 Regulates Salmonella-Containing Vacuole Biogenesis and Infection, CELL HOST & MICROBE, Vol: 17, Pages: 58-71, ISSN: 1931-3128

JOURNAL ARTICLE

Holden DW, 2015, Persisters unmasked, SCIENCE, Vol: 347, Pages: 30-32, ISSN: 0036-8075

JOURNAL ARTICLE

Mota J, Holden DW, Domingues L, 2014, The Salmonella effector SteA contributes to the control of membrane dynamics of Salmonella-containing vacuoles, FEBS EMBO 2014 Conference, Publisher: WILEY-BLACKWELL, Pages: 766-767, ISSN: 1742-464X

CONFERENCE PAPER

Xie H-X, Lu J-F, Rolhion N, Holden DW, Nie P, Zhou Y, Yu X-Jet al., 2014, Edwardsiella tarda-Induced Cytotoxicity Depends on Its Type III Secretion System and Flagellin, INFECTION AND IMMUNITY, Vol: 82, Pages: 3436-3445, ISSN: 0019-9567

JOURNAL ARTICLE

Domingues L, Holden DW, Mota LJ, 2014, The Salmonella Effector SteA Contributes to the Control of Membrane Dynamics of Salmonella-Containing Vacuoles, INFECTION AND IMMUNITY, Vol: 82, Pages: 2923-2934, ISSN: 0019-9567

JOURNAL ARTICLE

Helaine S, Cheverton AM, Watson KG, Faure LM, Matthews SA, Holden DWet al., 2014, Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters, SCIENCE, Vol: 343, Pages: 204-208, ISSN: 0036-8075

JOURNAL ARTICLE

Santos AJM, Meinecke M, Fessler MB, Holden DW, Boucrot Eet al., 2013, Preferential invasion of mitotic cells by Salmonella reveals that cell surface cholesterol is maximal during metaphase, JOURNAL OF CELL SCIENCE, Vol: 126, Pages: 2990-2996, ISSN: 0021-9533

JOURNAL ARTICLE

Helaine S, Holden DW, 2013, Heterogeneity of intracellular replication of bacterial pathogens, CURRENT OPINION IN MICROBIOLOGY, Vol: 16, Pages: 184-191, ISSN: 1369-5274

JOURNAL ARTICLE

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