Publications
128 results found
Mota J, Holden DW, Domingues L, 2014, The <i>Salmonella</i> effector SteA contributes to the control of membrane dynamics of <i>Salmonella</i>-containing vacuoles, FEBS EMBO 2014 Conference, Publisher: WILEY-BLACKWELL, Pages: 766-767, ISSN: 1742-464X
Xie H-X, Lu J-F, Rolhion N, et al., 2014, <i>Edwardsiella tarda</i>-Induced Cytotoxicity Depends on Its Type III Secretion System and Flagellin, INFECTION AND IMMUNITY, Vol: 82, Pages: 3436-3445, ISSN: 0019-9567
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- Citations: 29
Domingues L, Holden DW, Mota LJ, 2014, The <i>Salmonella</i> Effector SteA Contributes to the Control of Membrane Dynamics of <i>Salmonella</i>-Containing Vacuoles, INFECTION AND IMMUNITY, Vol: 82, Pages: 2923-2934, ISSN: 0019-9567
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- Citations: 30
Helaine S, Cheverton AM, Watson KG, et al., 2014, Internalization of salmonella by macrophages induces formation of nonreplicating persisters, SCIENCE, Vol: 343, Pages: 204-208, ISSN: 0036-8075
Many bacterial pathogens cause persistent infections despite repeated antibiotic exposure. Bacterial persisters are antibiotic-tolerant cells, but little is known about their growth status and the signals and pathways leading to their formation in infected tissues. We used fluorescent single-cell analysis to identify Salmonella persisters during infection. These were part of a nonreplicating population formed immediately after uptake by macrophages and were induced by vacuolar acidification and nutritional deprivation, conditions that also induce Salmonella virulence gene expression. The majority of 14 toxin-antitoxin modules contributed to intracellular persister formation. Some persisters resumed intracellular growth after phagocytosis by naïve macrophages. Thus, the vacuolar environment induces phenotypic heterogeneity, leading to either bacterial replication or the formation of nonreplicating persisters that could provide a reservoir for relapsing infection.
Santos AJM, Meinecke M, Fessler MB, et 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
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- Citations: 29
Figueira R, Watson KG, Holden DW, et al., 2013, Identification of salmonella pathogenicity island-2 type III secretion system effectors involved in intramacrophage replication of S. enterica serovar typhimurium: implications for rational vaccine design, mBio, Vol: 4, ISSN: 2161-2129
Salmonella enterica serovars cause severe diseases in humans, such as gastroenteritis and typhoid fever. The development of systemic disease is dependent on a type III secretion system (T3SS) encoded by Salmonella pathogenicity island-2 (SPI-2). Translocation of effector proteins across the Salmonella-containing vacuole, via the SPI-2 T3SS, enables bacterial replication within host cells, including macrophages. Here, we investigated the contribution of these effectors to intramacrophage replication of Salmonella enterica serovar Typhimurium using Fluorescence Dilution, a dual-fluorescence tool which allows direct measurement of bacterial replication. Of 32 strains, each carrying single mutations in genes encoding effectors, 10 (lacking sifA, sseJ, sopD2, sseG, sseF, srfH, sseL, spvD, cigR, or steD) were attenuated in replication in mouse bone marrow-derived macrophages. The replication profiles of strains combining deletions in effector genes were also investigated: a strain lacking the genes sseG, sopD2, and srfH showed an increased replication defect compared to single-mutation strains and was very similar to SPI-2 T3SS-deficient bacteria with respect to its replication defect. This strain was substantially attenuated in virulence in vivo and yet retained intracellular vacuole integrity and a functional SPI-2 T3SS. Moreover, this strain was capable of SPI-2 T3SS-mediated delivery of a model antigen for major histocompatibility complex (MHC) class I-dependent T-cell activation. This work establishes a basis for the use of a poly-effector mutant strain as an attenuated vaccine carrier for delivery of heterologous antigens directly into the cytoplasm of host cells.IMPORTANCE Live attenuated strains of Salmonella enterica serotype Typhi have generated much interest in the search for improved vaccines against typhoid fever and as vaccine vectors for the delivery of heterologous antigens. A promising vaccine candidate is the ΔaroC ΔssaV S. Typhi strain, whic
Helaine S, Holden DW, 2013, Heterogeneity of intracellular replication of bacterial pathogens, CURRENT OPINION IN MICROBIOLOGY, Vol: 16, Pages: 184-191, ISSN: 1369-5274
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- Citations: 45
Mesquita FS, Holden DW, Rolhion N, 2013, Lack of Effect of the <i>Salmonella</i> Deubiquitinase SseL on the NF-κB Pathway, PLOS ONE, Vol: 8, ISSN: 1932-6203
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- Citations: 17
Thomas M, Mesquita FS, Holden DW, 2012, The DUB-ious lack of ALIS in Salmonella infection A Salmonella deubiquitinase regulates the autophagy of protein aggregates, AUTOPHAGY, Vol: 8, Pages: 1824-1826, ISSN: 1554-8627
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- Citations: 17
McGourty K, Thurston TLM, Matthews SA, et al., 2012, Salmonella inhibits retrograde trafficking of mannose-6-phosphate receptors and lysosome function., Science
Odendall C, Rolhion N, Foerster A, et al., 2012, The <i>Salmonella</i> Kinase SteC Targets the MAP Kinase MEK to Regulate the Host Actin Cytoskeleton, CELL HOST & MICROBE, Vol: 12, Pages: 657-668, ISSN: 1931-3128
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- Citations: 60
Dart AE, Donnelly SK, Holden DW, et al., 2012, Nck and Cdc42 co-operate to recruit N-WASP to promote FcγR-mediated phagocytosis, JOURNAL OF CELL SCIENCE, Vol: 125, Pages: 2825-2830, ISSN: 0021-9533
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- Citations: 31
Mesquita FS, Thomas M, Sachse M, et al., 2012, The <i>Salmonella</i> Deubiquitinase SseL Inhibits Selective Autophagy of Cytosolic Aggregates, PLOS PATHOGENS, Vol: 8, ISSN: 1553-7366
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- Citations: 121
Figueira R, Holden DW, 2012, Functions of the <i>Salmonella</i> pathogenicity island 2 (SPI-2) type III secretion system effectors, MICROBIOLOGY-SGM, Vol: 158, Pages: 1147-1161, ISSN: 1350-0872
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- Citations: 246
Yu X-J, Liu M, Matthews S, et al., 2011, Tandem Translation Generates a Chaperone for the <i>Salmonella</i> Type III Secretion System Protein SsaQ, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 36098-36107
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- Citations: 29
Thompson JA, Liu M, Helainet S, et al., 2011, Contribution of the PhoP/Q regulon to survival and replication of <i>Salmonella enterica</i> serovar Typhimurium in macrophages, MICROBIOLOGY-SGM, Vol: 157, Pages: 2084-2093, ISSN: 1350-0872
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- Citations: 39
Watson KG, Holden DW, 2010, Dynamics of growth and dissemination of <i>Salmonella in vivo</i>, CELLULAR MICROBIOLOGY, Vol: 12, Pages: 1389-1397, ISSN: 1462-5814
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- Citations: 97
Dumont A, Boucrot E, Drevensek S, et al., 2010, SKIP, the Host Target of the <i>Salmonella</i> Virulence Factor SifA, Promotes Kinesin-1-Dependent Vacuolar Membrane Exchanges, TRAFFIC, Vol: 11, Pages: 899-911, ISSN: 1398-9219
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- Citations: 82
Yu X-J, McGourty K, Liu M, et al., 2010, pH Sensing by Intracellular <i>Salmonella</i> Induces Effector Translocation, SCIENCE, Vol: 328, Pages: 1040-1043, ISSN: 0036-8075
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- Citations: 137
Helaine S, Thompson JA, Watson KG, et al., 2010, Dynamics of intracellular bacterial replication at the single cell level, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 3746-3751, ISSN: 0027-8424
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- Citations: 222
Groves E, Rittinger K, Amstutz M, et al., 2010, Sequestering of Rac by the <i>Yersinia</i> Effector YopO Blocks Fcγ Receptor-mediated Phagocytosis, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 285, Pages: 4087-4098
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- Citations: 34
Lapaque N, Hutchinson JL, Jones DC, et al., 2009, Salmonella regulates polyubiquitination and surface expression of MHC class II antigens, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 106, Pages: 14052-14057, ISSN: 0027-8424
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- Citations: 62
Mota LJ, Ramsden AE, Liu M, et al., 2009, SCAMP3 is a component of the <i>Salmonella</i>-induced tubular network and reveals an interaction between bacterial effectors and post-Golgi trafficking, CELLULAR MICROBIOLOGY, Vol: 11, Pages: 1236-1253, ISSN: 1462-5814
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- Citations: 60
Thomas M, Holden DW, 2009, Ubiquitination-A Bacterial Effector's Ticket to Ride, CELL HOST & MICROBE, Vol: 5, Pages: 309-311, ISSN: 1931-3128
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- Citations: 7
Lossi NS, Rolhion N, Magee AI, et al., 2008, The <i>Salmonella</i> SPI-2 effector SseJ exhibits eukaryotic activator-dependent phospholipase A and glycerophospholipid:: cholesterol acyltransferase activity, MICROBIOLOGY-SGM, Vol: 154, Pages: 2680-2688, ISSN: 1350-0872
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- Citations: 62
Mazurkiewicz P, Thomas J, Thompson JA, et al., 2008, SpvC is a Salmonella effector with phosphothreonine lyase activity on host mitogen-activated protein kinases, Molecular Microbiology, Vol: 67, Pages: 1371-1383, ISSN: 1365-2958
SpvC is encoded by the Salmonella virulence plasmid. We have investigated the biochemical function of SpvC and the mechanism by which it is secreted by bacteria and translocated into infected macrophages. We constructed a strain carrying a deletion in spvC and showed that the strain is attenuated for systemic virulence in mice. SpvC can be secreted in vitro by either the SPI-1 or SPI-2 type III secretion systems. Cell biological and genetic experiments showed that translocation of the protein into the cytosol of macrophages by intracellular bacteria is dependent on the SPI-2 T3SS. Using antibodies specific to phospho-amino acids and mass spectrometry we demonstrate that SpvC has phosphothreonine lyase activity on full-length phospho-Erk (pErk) and a synthetic 13-amino-acid phospho-peptide containing the TXY motif. A Salmonella strain expressing spvC from a plasmid downregulated cytokine release from infected cells.
Poh J, Odendall C, Spanos A, et al., 2008, SteC is a Salmonella kinase required for SPI-2-dependent F-actin remodelling, Cellular Microbiology, Vol: 10, Pages: 20-30, ISSN: 1462-5814
Salmonella enterica serovar Typhimurium (S. Typhimurium) replicates inside mammalian cells within membrane‐bound compartments called Salmonella‐containing vacuoles. Intracellular replication is dependent on the activities of several effector proteins translocated across the vacuolar membrane by the Salmonella pathogenicity island 2 (SPI‐2)‐type III secretion system (T3SS). This is accompanied by the formation in the vicinity of bacterial vacuoles of an F‐actin meshwork, thought to be involved in maintaining the integrity of vacuolar membranes. In this study, we investigated the function of the SPI‐2 T3SS effector SteC. An steC mutant strain was not defective for intracellular replication or attenuated for virulence in mice. However, the steC mutant was defective for SPI‐2‐dependent F‐actin meshwork formation in host cells, although the vacuolar membranes surrounding mutant bacteria appeared to be normal. Expression of SteC in fibroblast cells following transfection caused extensive rearrangements of the F‐actin cytoskeleton. Sequence analysis identified amino acid similarity between SteC and the human kinase Raf‐1. A His‐tagged SteC fusion protein had kinase activity in vitro and a point mutant lacking kinase activity was unable to induce F‐actin rearrangements in vivo. We conclude that SPI‐2‐dependent F‐actin meshwork formation depends on the kinase activity of SteC, which resembles more closely eukaryotic than prokaryotic kinases.
Ramsden AE, Holden DW, Mota LJ, 2007, Membrane dynamics and spatial distribution of <i>Salmonella</i>-containing vacuoles, TRENDS IN MICROBIOLOGY, Vol: 15, Pages: 516-524, ISSN: 0966-842X
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- Citations: 60
Nelson AL, Ries J, Bagnoli F, et al., 2007, RrgA is a pilus-associated adhesin in <i>Streptococcus pneumoniae</i>, MOLECULAR MICROBIOLOGY, Vol: 66, Pages: 329-340, ISSN: 0950-382X
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- Citations: 134
Ramsden AE, Mota LJ, Muenter S, et al., 2007, The SPI-2 type III secretion system restricts motility of <i>Salmonella</i>-containing vacuoles, CELLULAR MICROBIOLOGY, Vol: 9, Pages: 2517-2529, ISSN: 1462-5814
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- Citations: 55
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