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

Holden DW, Errington J, 2018, Type II Toxin-Antitoxin Systems and Persister Cells., MBio, Vol: 9

JOURNAL ARTICLE

Yu X-J, Grabe GJ, Liu M, Mota LJ, Holden DWet al., 2018, SsaV Interacts with SsaL to Control the Translocon-to-Effector Switch in the Salmonella SPI-2 Type Three Secretion System., MBio, Vol: 9

Nonflagellar type III secretion systems (nf T3SSs) form a cell surface needle-like structure and an associated translocon that deliver bacterial effector proteins into eukaryotic host cells. This involves a tightly regulated hierarchy of protein secretion. A switch involving SctP and SctU stops secretion of the needle protein. The gatekeeper protein SctW is required for secretion of translocon proteins and controls a second switch to start effector secretion. Salmonella enterica serovar Typhimurium encodes two T3SSs in Salmonella pathogenicity island 1 (SPI-1) and SPI-2. The acidic vacuole containing intracellular bacteria stimulates assembly of the SPI-2 T3SS and its translocon. Sensing the nearly neutral host cytosolic pH is required for effector translocation. Here, we investigated the involvement of SPI-2-encoded proteins SsaP (SctP), SsaU (SctU), SsaV (SctV), and SsaL (SctW) in regulation of secretion. We found that SsaP and SsaU are involved in the first but not the second secretion switch. A random-mutagenesis screen identified amino acids of SsaV that regulate translocon and effector secretion. Single substitutions in subdomain 4 of SsaV or InvA (SPI-1-encoded SctV) phenocopied mutations of their corresponding gatekeepers with respect to translocon and effector protein secretion and host cell interactions. SsaL interacted with SsaV in bacteria exposed to low ambient pH but not after the pH was raised to 7.2. We propose that SsaP and SsaU enable the apparatus to become competent for a secretion switch and facilitate the SsaL-SsaV interaction. This mediates secretion of translocon proteins until neutral pH is sensed, which causes their dissociation, resulting in arrest of translocon secretion and derepression of effector translocation.IMPORTANCESalmonella Typhimurium is an intracellular pathogen that uses the SPI-2 type III secretion system to deliver virulence proteins across the vacuole membrane surrounding intracellular bacteria. This involves a tightly reg

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

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

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

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

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, MBIO, Vol: 7, ISSN: 2150-7511

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

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

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

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

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

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

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

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

JOURNAL ARTICLE

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

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

Thurston TLM, holden DW, 2015, interactions between salmonella and the autophagy system, Autophagy, infection, and the immune response, Editors: jackson, swanson, Publisher: Wiley Blackwell, ISBN: 978-1-118-67764-3

BOOK CHAPTER

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

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

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

Mesquita FS, Holden DW, Rolhion N, 2013, Lack of Effect of the Salmonella Deubiquitinase SseL on the NF-kappa B Pathway, PLOS ONE, Vol: 8, ISSN: 1932-6203

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

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