Publications

Search or filter publications

Search publications Search

Filter by type:

Filter by publication type

• Book
• Book chapter
• Conference paper
• Journal article
• Patent
• Report
• Software

Filter by year:

Filter from 20232022202120202019201820172016201520142013 to Filter to 20232022202120202019201820172016201520142013

---

Search results

• Journal article
  Rasheed M, Garnett J, Perez-Dorado I, Muhl D, Filloux A, Matthews Set al., 2016,

  Crystal structure of the CupB6 adhesive tip from the chaperone-usher family of pili from Pseudomonas aeruginosa

  , Biochimica et Biophysica Acta - Protein Structure, Vol: 1864, Pages: 1500-1505, ISSN: 0005-2795

  Pseudomonas aeruginosa is a Gram-negative opportunistic bacterial pathogen that can cause chronicinfection of the lungs of cystic fibrosis patients. Chaperone-usher systems in P. aeruginosa are knownto translocate and assemble adhesive pili on the bacterial surface and contribute to biofilm formationwithin the host. Here, we report the crystal structure of the tip adhesion subunit CupB6 from thecupB1-6 gene cluster. The tip domain is connected to the pilus via the N-terminal donor strand fromthe main pilus subunit CupB1. Although the CupB6 adhesion domain bears structural features similarto other CU adhesins it displays an unusual polyproline helix adjacent to a prominent surface pocket,which are likely the site for receptor recognition.

  • Abstract
  • Open Access Link
  • Cite
• Journal article
  Kierdorf K, Dionne MS, 2016,

  The software and hardware of macrophages: a diversity of options

  , Developmental Cell, Vol: 38, Pages: 122-125, ISSN: 1878-1551

  Macrophages play important immune and homeostatic roles that depend on the ability to receive and interpret specific signals from environmental stimuli. Here we describe the different activation states these cells can exhibit in response to signals and how these states affect and can be affected by bacterial pathogens.

  • Abstract
  • Open Access Link
  • Cite
• 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

  Pathogenic bacteria rely on secreted effector proteins to manipulate host signaling pathways, often in creative ways. CE clan proteases, specific hydrolases for ubiquitin-like modifications (SUMO and NEDD8) in eukaryotes, reportedly serve as bacterial effector proteins with deSUMOylase, deubiquitinase, or, even, acetyltransferase activities. Here, we characterize bacterial CE protease activities, revealing K63-linkage-specific deubiquitinases in human pathogens, such as Salmonella, Escherichia, and Shigella, as well as ubiquitin/ubiquitin-like cross-reactive enzymes in Chlamydia, Rickettsia, and Xanthomonas. Five crystal structures, including ubiquitin/ubiquitin-like complexes, explain substrate specificities and redefine relationships across the CE clan. Importantly, this work identifies novel family members and provides key discoveries among previously reported effectors, such as the unexpected deubiquitinase activity in Xanthomonas XopD, contributed by an unstructured ubiquitin binding region. Furthermore, accessory domains regulate properties such as subcellular localization, as exemplified by a ubiquitin-binding domain in Salmonella Typhimurium SseL. Our work both highlights and explains the functional adaptations observed among diverse CE clan proteins.

  • Abstract
  • Open Access Link
  • Cite
• Journal article
  Yu XJ, Liu M, Holden D, 2016,

  Salmonella Effectors SseF and SseG Interact with Mammalian Protein ACBD3 (GCP60) To Anchor Salmonella-Containing Vacuoles at the Golgi Network

  , mBio, Vol: 7, ISSN: 2161-2129

  Following infection of mammalian cells, Salmonella enterica serovar Typhimurium (S. Typhimurium) replicates within membrane-bound compartments known as Salmonella-containing vacuoles (SCVs). The Salmonella pathogenicity island 2 type III secretion system (SPI-2 T3SS) translocates approximately 30 different effectors across the vacuolar membrane. SseF and SseG are two such effectors that are required for SCVs to localize close to the Golgi network in infected epithelial cells. In a yeast two-hybrid assay, SseG and an N-terminal variant of SseF interacted directly with mammalian ACBD3, a multifunctional cytosolic Golgi network-associated protein. Knockdown of ACBD3 by small interfering RNA (siRNA) reduced epithelial cell Golgi network association of wild-type bacteria, phenocopying the effect of null mutations of sseG or sseF. Binding of SseF to ACBD3 in infected cells required the presence of SseG. A single-amino-acid mutant of SseG and a double-amino-acid mutant of SseF were obtained that did not interact with ACBD3 in Saccharomyces cerevisiae. When either of these was produced together with the corresponding wild-type effector by Salmonella in infected cells, they enabled SCV-Golgi network association and interacted with ACBD3. However, these properties were lost and bacteria displayed an intracellular replication defect when cells were infected with Salmonella carrying both mutant genes. Knockdown of ACBD3 resulted in a replication defect of wild-type bacteria but did not further attenuate the growth defect of a ΔsseFG mutant strain. We propose a model in which interaction between SseF and SseG enables both proteins to bind ACBD3, thereby anchoring SCVs at the Golgi network and facilitating bacterial replication.

  • Abstract
  • Open Access Link
  • Cite
• Journal article
  Sirianni A, Krokowski S, Lobato-Márquez D, Buranyi S, Pfanzelter J, Galea D, Willis A, Culley S, Henriques R, Larrouy-Maumus G, Hollinshead M, Sancho-Shimizu V, Way M, Mostowy Set al., 2016,

  Mitochondria mediate septin cage assembly to promote autophagy of Shigella

  , EMBO Reports, Vol: 17, Pages: 1-15, ISSN: 1469-221X

  Septins, cytoskeletal proteins with well-characterised roles in cytokinesis, form cage-like structures around cytosolic Shigella flexneri and promote their targeting to autophagosomes. However, the processes underlying septin cage assembly, and whether they influence S. flexneri proliferation, remain to be established. Using single cell analysis, we show that septin cages inhibit S. flexneri proliferation. To study mechanisms of septin cage assembly, we used proteomics and found mitochondrial proteins associate with septins in S. flexneriinfected cells. Strikingly, mitochondria associated with S. flexneri promote septin assembly into the cages that entrap bacteria for autophagy. We demonstrate that the cytosolic GTPase dynamin-related protein 1 (Drp1) interacts with septins to enhance mitochondrial fission. To avoid autophagy, actin-polymerising Shigella fragment mitochondria to escape from septin caging. Our results have demonstrated a role for mitochondria in anti-Shigella autophagy, and uncovered a fundamental link between septin assembly and mitochondria.

  • Abstract
  • Publisher Web Link
  • Open Access Link
  • Cite
• Journal article
  Cheverton AM, Gollan B, Przydacz M, Wong CT, Mylona A, Hare SA, Helaine Set al., 2016,

  A Salmonella Toxin Promotes Persister Formation through Acetylation of tRNA.

  , Molecular cell, Vol: 63, Pages: 86-96, ISSN: 1097-2765

  The recalcitrance of many bacterial infections to antibiotic treatment is thought to be due to the presence of persisters that are non-growing, antibiotic-insensitive cells. Eventually, persisters resume growth, accounting for relapses of infection. Salmonella is an important pathogen that causes disease through its ability to survive inside macrophages. After macrophage phagocytosis, a significant proportion of the Salmonella population forms non-growing persisters through the action of toxin-antitoxin modules. Here we reveal that one such toxin, TacT, is an acetyltransferase that blocks the primary amine group of amino acids on charged tRNA molecules, thereby inhibiting translation and promoting persister formation. Furthermore, we report the crystal structure of TacT and note unique structural features, including two positively charged surface patches that are essential for toxicity. Finally, we identify a detoxifying mechanism in Salmonella wherein peptidyl-tRNA hydrolase counteracts TacT-dependent growth arrest, explaining how bacterial persisters can resume growth.

  • Abstract
  • Open Access Link
  • Cite
  • Citations: 134
• Journal article
  O'Neill AM, Thurston TL, Holden DW, 2016,

  Erratum for O'Neill et al., Cytosolic Replication of Group A Streptococcus in Human Macrophages.

  , mBio, Vol: 7, ISSN: 2161-2129
  • Open Access Link
  • Cite
• Journal article
  Filloux A, Freemont P, 2016,

  Structural biology: baseplates in contractile machines

  , Nature Microbiology, Vol: 1, ISSN: 2058-5276
  • Open Access Link
  • Cite
• Journal article
  Taglialegna A, Navarro S, Ventura S, Garnett JA, Matthews S, Penades JR, Lasa I, Valle Jet al., 2016,

  Staphylococcal Bap Proteins Build Amyloid Scaffold Biofilm Matrices in Response to Environmental Signals

  , PLOS Pathogens, Vol: 12, ISSN: 1553-7366

  Biofilms are communities of bacteria that grow encased in an extracellular matrix that often contains proteins. The spatial organization and the molecular interactions between matrix scaffold proteins remain in most cases largely unknown. Here, we report that Bap protein of Staphylococcus aureus self-assembles into functional amyloid aggregates to build the biofilm matrix in response to environmental conditions. Specifically, Bap is processed and fragments containing at least the N-terminus of the protein become aggregation-prone and self-assemble into amyloid-like structures under acidic pHs and low concentrations of calcium. The molten globule-like state of Bap fragments is stabilized upon binding of the cation, hindering its self-assembly into amyloid fibers. These findings define a dual function for Bap, first as a sensor and then as a scaffold protein to promote biofilm development under specific environmental conditions. Since the pH-driven multicellular behavior mediated by Bap occurs in coagulase-negative staphylococci and many other bacteria exploit Bap-like proteins to build a biofilm matrix, the mechanism of amyloid-like aggregation described here may be widespread among pathogenic bacteria.

  • Abstract
  • Open Access Link
  • Cite
• Journal article
  Planamente S, Salih O, Manoli E, Albesa-Jove D, Freemont PS, Filloux AAMet al., 2016,

  TssA forms a gp6-like ring attached to the type VI secretion sheath

  , EMBO Journal, Vol: 35, Pages: 1613-1627, ISSN: 0261-4189

  The type VI secretion system (T6SS) is a supra-molecular bacterial complex that resembles phage tails. It is a killing machine which fires toxins into target cells upon contraction of its TssBC sheath. Here, we show that TssA1 is a T6SS component forming dodecameric ring structures whose dimensions match those of the TssBC sheath and which can accommodate the inner Hcp tube. The TssA1 ring complex binds the T6SS sheath and impacts its behaviour in vivo. In the phage, the first disc of the gp18 sheath sits on a baseplate wherein gp6 is a dodecameric ring. We found remarkable sequence and structural similarities between TssA1 and gp6 C-termini, and propose that TssA1 could be a baseplate component of the T6SS. Furthermore, we identified similarities between TssK1 and gp8, the former interacting with TssA1 while the latter is found in the outer radius of the gp6 ring. These observations, combined with similarities between TssF and gp6N-terminus or TssG and gp53, lead us to propose a comparative model between the phage baseplate and the T6SS.

  • Abstract
  • Open Access Link
  • Cite

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.