Structural and Functional Characterization of the Bacterial Type III Secretion Export Apparatus.

Abstract:

:Bacterial type III protein secretion systems inject effector proteins into eukaryotic host cells in order to promote survival and colonization of Gram-negative pathogens and symbionts. Secretion across the bacterial cell envelope and injection into host cells is facilitated by a so-called injectisome. Its small hydrophobic export apparatus components SpaP and SpaR were shown to nucleate assembly of the needle complex and to form the central "cup" substructure of a Salmonella Typhimurium secretion system. However, the in vivo placement of these components in the needle complex and their function during the secretion process remained poorly defined. Here we present evidence that a SpaP pentamer forms a 15 Å wide pore and provide a detailed map of SpaP interactions with the export apparatus components SpaQ, SpaR, and SpaS. We further refine the current view of export apparatus assembly, consolidate transmembrane topology models for SpaP and SpaR, and present intimate interactions of the periplasmic domains of SpaP and SpaR with the inner rod protein PrgJ, indicating how export apparatus and needle filament are connected to create a continuous conduit for substrate translocation.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Dietsche T,Tesfazgi Mebrhatu M,Brunner MJ,Abrusci P,Yan J,Franz-Wachtel M,Schärfe C,Zilkenat S,Grin I,Galán JE,Kohlbacher O,Lea S,Macek B,Marlovits TC,Robinson CV,Wagner S

doi

10.1371/journal.ppat.1006071

subject

Has Abstract

pub_date

2016-12-15 00:00:00

pages

e1006071

issue

12

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-16-02083

journal_volume

12

pub_type

杂志文章
  • A multi-step process of viral adaptation to a mutagenic nucleoside analogue by modulation of transition types leads to extinction-escape.

    abstract::Resistance of viruses to mutagenic agents is an important problem for the development of lethal mutagenesis as an antiviral strategy. Previous studies with RNA viruses have documented that resistance to the mutagenic nucleoside analogue ribavirin (1-β-D-ribofuranosyl-1-H-1,2,4-triazole-3-carboxamide) is mediated by am...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001072

    authors: Agudo R,Ferrer-Orta C,Arias A,de la Higuera I,Perales C,Pérez-Luque R,Verdaguer N,Domingo E

    更新日期:2010-08-26 00:00:00

  • Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions.

    abstract::The HIV-1 envelope glycoprotein (Env) composed of the receptor binding domain gp120 and the fusion protein subunit gp41 catalyzes virus entry and is a major target for therapeutic intervention and for neutralizing antibodies. Env interactions with cellular receptors trigger refolding of gp41, which induces close appos...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000880

    authors: Buzon V,Natrajan G,Schibli D,Campelo F,Kozlov MM,Weissenhorn W

    更新日期:2010-05-06 00:00:00

  • Ex vivo activation of CD4+ T-cells from donors on suppressive ART can lead to sustained production of infectious HIV-1 from a subset of infected cells.

    abstract::The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006230

    authors: Bui JK,Halvas EK,Fyne E,Sobolewski MD,Koontz D,Shao W,Luke B,Hong FF,Kearney MF,Mellors JW

    更新日期:2017-02-22 00:00:00

  • Forward genetic screening identifies a small molecule that blocks Toxoplasma gondii growth by inhibiting both host- and parasite-encoded kinases.

    abstract::The simultaneous targeting of host and pathogen processes represents an untapped approach for the treatment of intracellular infections. Hypoxia-inducible factor-1 (HIF-1) is a host cell transcription factor that is activated by and required for the growth of the intracellular protozoan parasite Toxoplasma gondii at p...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004180

    authors: Brown KM,Suvorova E,Farrell A,McLain A,Dittmar A,Wiley GB,Marth G,Gaffney PM,Gubbels MJ,White M,Blader IJ

    更新日期:2014-06-12 00:00:00

  • The M/GP(5) glycoprotein complex of porcine reproductive and respiratory syndrome virus binds the sialoadhesin receptor in a sialic acid-dependent manner.

    abstract::The porcine reproductive and respiratory syndrome virus (PRRSV) is a major threat to swine health worldwide and is considered the most significant viral disease in the swine industry today. In past years, studies on the entry of the virus into its host cell have led to the identification of a number of essential virus...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000730

    authors: Van Breedam W,Van Gorp H,Zhang JQ,Crocker PR,Delputte PL,Nauwynck HJ

    更新日期:2010-01-15 00:00:00

  • A Toxoplasma palmitoyl acyl transferase and the palmitoylated armadillo repeat protein TgARO govern apical rhoptry tethering and reveal a critical role for the rhoptries in host cell invasion but not egress.

    abstract::Apicomplexans are obligate intracellular parasites that actively penetrate their host cells to create an intracellular niche for replication. Commitment to invasion is thought to be mediated by the rhoptries, specialized apical secretory organelles that inject a protein complex into the host cell to form a tight-junct...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003162

    authors: Beck JR,Fung C,Straub KW,Coppens I,Vashisht AA,Wohlschlegel JA,Bradley PJ

    更新日期:2013-02-01 00:00:00

  • Dual pili post-translational modifications synergize to mediate meningococcal adherence to platelet activating factor receptor on human airway cells.

    abstract::Pili of pathogenic Neisseria are major virulence factors associated with adhesion, twitching motility, auto-aggregation, and DNA transformation. Pili of N. meningitidis are subject to several different post-translational modifications. Among these pilin modifications, the presence of phosphorylcholine (ChoP) and a gly...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003377

    authors: Jen FE,Warren MJ,Schulz BL,Power PM,Swords WE,Weiser JN,Apicella MA,Edwards JL,Jennings MP

    更新日期:2013-01-01 00:00:00

  • Correction: The secreted peptide PIP1 amplifies immunity through receptor-like kinase 7.

    abstract::[This corrects the article DOI: 10.1371/journal.ppat.1004331.]. ...

    journal_title:PLoS pathogens

    pub_type: 已发布勘误

    doi:10.1371/journal.ppat.1004710

    authors: PLOS Pathogens Staff.

    更新日期:2015-02-19 00:00:00

  • Environmental constraints guide migration of malaria parasites during transmission.

    abstract::Migrating cells are guided in complex environments mainly by chemotaxis or structural cues presented by the surrounding tissue. During transmission of malaria, parasite motility in the skin is important for Plasmodium sporozoites to reach the blood circulation. Here we show that sporozoite migration varies in differen...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002080

    authors: Hellmann JK,Münter S,Kudryashev M,Schulz S,Heiss K,Müller AK,Matuschewski K,Spatz JP,Schwarz US,Frischknecht F

    更新日期:2011-06-01 00:00:00

  • ChIP-seq and in vivo transcriptome analyses of the Aspergillus fumigatus SREBP SrbA reveals a new regulator of the fungal hypoxia response and virulence.

    abstract::The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence i...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004487

    authors: Chung D,Barker BM,Carey CC,Merriman B,Werner ER,Lechner BE,Dhingra S,Cheng C,Xu W,Blosser SJ,Morohashi K,Mazurie A,Mitchell TK,Haas H,Mitchell AP,Cramer RA

    更新日期:2014-11-06 00:00:00

  • Viral and cellular proteins containing FGDF motifs bind G3BP to block stress granule formation.

    abstract::The Ras-GAP SH3 domain-binding proteins (G3BP) are essential regulators of the formation of stress granules (SG), cytosolic aggregates of proteins and RNA that are induced upon cellular stress, such as virus infection. Many viruses, including Semliki Forest virus (SFV), block SG induction by targeting G3BP. In this wo...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004659

    authors: Panas MD,Schulte T,Thaa B,Sandalova T,Kedersha N,Achour A,McInerney GM

    更新日期:2015-02-06 00:00:00

  • The Legionella pneumophila effector VipA is an actin nucleator that alters host cell organelle trafficking.

    abstract::Legionella pneumophila, the causative agent of Legionnaires' disease, invades and replicates within macrophages and protozoan cells inside a vacuole. The type IVB Icm/Dot secretion system is necessary for the translocation of effector proteins that modulate vesicle trafficking pathways in the host cell, thus avoiding ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002546

    authors: Franco IS,Shohdy N,Shuman HA

    更新日期:2012-02-01 00:00:00

  • Type VI Secretion System Toxins Horizontally Shared between Marine Bacteria.

    abstract::The type VI secretion system (T6SS) is a widespread protein secretion apparatus used by Gram-negative bacteria to deliver toxic effector proteins into adjacent bacterial or host cells. Here, we uncovered a role in interbacterial competition for the two T6SSs encoded by the marine pathogen Vibrio alginolyticus. Using c...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005128

    authors: Salomon D,Klimko JA,Trudgian DC,Kinch LN,Grishin NV,Mirzaei H,Orth K

    更新日期:2015-08-25 00:00:00

  • AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in-vivo following pandemic 2009-H1N1 vaccination in humans.

    abstract::The role of Activation-Induced Cytidine Deaminase (AID) in somatic hypermutation and polyclonal antibody affinity maturation has not been shown for polyclonal responses in humans. We investigated whether AID induction in human B cells following H1N1pdm09 vaccination correlated with in-vivo antibody affinity maturation...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002920

    authors: Khurana S,Frasca D,Blomberg B,Golding H

    更新日期:2012-09-01 00:00:00

  • Highly competent, non-exhausted CD8+ T cells continue to tightly control pathogen load throughout chronic Trypanosoma cruzi infection.

    abstract::Trypanosoma cruzi infection is characterized by chronic parasitism of non-lymphoid tissues and is rarely eliminated despite potent adaptive immune responses. This failure to cure has frequently been attributed to a loss or impairment of anti-T. cruzi T cell responses over time, analogous to the T cell dysfunction desc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007410

    authors: Pack AD,Collins MH,Rosenberg CS,Tarleton RL

    更新日期:2018-11-12 00:00:00

  • Correction: Persistent mycobacteria evade an antibacterial program mediated by phagolysosomal TLR7/8/MyD88 in human primary macrophages.

    abstract::[This corrects the article DOI: 10.1371/journal.ppat.1006551.]. ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,已发布勘误

    doi:10.1371/journal.ppat.1006712

    authors: Gidon A,Åsberg SE,Louet C,Ryan L,Haug M,Flo TH

    更新日期:2017-11-07 00:00:00

  • Novel escape mutants suggest an extensive TRIM5α binding site spanning the entire outer surface of the murine leukemia virus capsid protein.

    abstract::After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5α. While it is clear that these factors target retrovirus capsid proteins (CA), recognition remains poorly defined in the absence of structural information. To better understand the binding interaction between TRIM5...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002011

    authors: Ohkura S,Goldstone DC,Yap MW,Holden-Dye K,Taylor IA,Stoye JP

    更新日期:2011-03-01 00:00:00

  • Correction: A model of chronic, transmissible Otitis Media in mice.

    abstract::[This corrects the article DOI: 10.1371/journal.ppat.1007696.]. ...

    journal_title:PLoS pathogens

    pub_type: 已发布勘误

    doi:10.1371/journal.ppat.1007916

    authors: Dewan KK,Taylor-Mulneix DL,Campos LL,Skarlupka AL,Wagner SM,Ryman VE,Gestal MC,Ma L,Blas-Machado U,Faddis BT,Harvill ET

    更新日期:2019-06-28 00:00:00

  • HIV-1 buds predominantly at the plasma membrane of primary human macrophages.

    abstract::HIV-1 assembly and release are believed to occur at the plasma membrane in most host cells with the exception of primary macrophages, for which exclusive budding at late endosomes has been reported. Here, we applied a novel ultrastructural approach to assess HIV-1 budding in primary macrophages in an immunomarker-inde...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030036

    authors: Welsch S,Keppler OT,Habermann A,Allespach I,Krijnse-Locker J,Kräusslich HG

    更新日期:2007-03-01 00:00:00

  • The Structural Architecture of an Infectious Mammalian Prion Using Electron Cryomicroscopy.

    abstract::The structure of the infectious prion protein (PrPSc), which is responsible for Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, has escaped all attempts at elucidation due to its insolubility and propensity to aggregate. PrPSc replicates by converting the non-infectious, cellular prion protei...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005835

    authors: Vázquez-Fernández E,Vos MR,Afanasyev P,Cebey L,Sevillano AM,Vidal E,Rosa I,Renault L,Ramos A,Peters PJ,Fernández JJ,van Heel M,Young HS,Requena JR,Wille H

    更新日期:2016-09-08 00:00:00

  • Phosphoinositide-3 kinase-Akt pathway controls cellular entry of Ebola virus.

    abstract::The phosphoinositide-3 kinase (PI3K) pathway regulates diverse cellular activities related to cell growth, migration, survival, and vesicular trafficking. It is known that Ebola virus requires endocytosis to establish an infection. However, the cellular signals that mediate this uptake were unknown for Ebola virus as ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000141

    authors: Saeed MF,Kolokoltsov AA,Freiberg AN,Holbrook MR,Davey RA

    更新日期:2008-08-29 00:00:00

  • Adhesion of Neisseria meningitidis to dermal vessels leads to local vascular damage and purpura in a humanized mouse model.

    abstract::Septic shock caused by Neisseria meningitidis is typically rapidly evolving and often fatal despite antibiotic therapy. Further understanding of the mechanisms underlying the disease is necessary to reduce fatality rates. Postmortem samples from the characteristic purpuric rashes of the infection show bacterial aggreg...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003139

    authors: Melican K,Michea Veloso P,Martin T,Bruneval P,Duménil G

    更新日期:2013-01-01 00:00:00

  • αvβ6- and αvβ8-integrins serve as interchangeable receptors for HSV gH/gL to promote endocytosis and activation of membrane fusion.

    abstract::Herpes simplex virus (HSV)--and herpesviruses in general--encode for a multipartite entry/fusion apparatus. In HSV it consists of the HSV-specific glycoprotein D (gD), and three additional glycoproteins, gH/gL and gB, conserved across the Herpesviridae family and responsible for the execution of fusion. According to t...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003806

    authors: Gianni T,Salvioli S,Chesnokova LS,Hutt-Fletcher LM,Campadelli-Fiume G

    更新日期:2013-01-01 00:00:00

  • Polarized Cell Division of Chlamydia trachomatis.

    abstract::Bacterial cell division predominantly occurs by a highly conserved process, termed binary fission, that requires the bacterial homologue of tubulin, FtsZ. Other mechanisms of bacterial cell division that are independent of FtsZ are rare. Although the obligate intracellular human pathogen Chlamydia trachomatis, the lea...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005822

    authors: Abdelrahman Y,Ouellette SP,Belland RJ,Cox JV

    更新日期:2016-08-09 00:00:00

  • Immunization against a saccharide epitope accelerates clearance of experimental gonococcal infection.

    abstract::The emergence of ceftriaxone-resistant strains of Neisseria gonorrhoeae may herald an era of untreatable gonorrhea. Vaccines against this infection are urgently needed. The 2C7 epitope is a conserved oligosaccharide (OS) structure, a part of lipooligosaccharide (LOS) on N gonorrhoeae. The epitope is expressed by 94% o...

    journal_title:PLoS pathogens

    pub_type: 临床试验,杂志文章

    doi:10.1371/journal.ppat.1003559

    authors: Gulati S,Zheng B,Reed GW,Su X,Cox AD,St Michael F,Stupak J,Lewis LA,Ram S,Rice PA

    更新日期:2013-01-01 00:00:00

  • A nasal epithelial receptor for Staphylococcus aureus WTA governs adhesion to epithelial cells and modulates nasal colonization.

    abstract::Nasal colonization is a major risk factor for S. aureus infections. The mechanisms responsible for colonization are still not well understood and involve several factors on the host and the bacterial side. One key factor is the cell wall teichoic acid (WTA) of S. aureus, which governs direct interactions with nasal ep...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004089

    authors: Baur S,Rautenberg M,Faulstich M,Grau T,Severin Y,Unger C,Hoffmann WH,Rudel T,Autenrieth IB,Weidenmaier C

    更新日期:2014-05-01 00:00:00

  • Kinetics of HTLV-1 reactivation from latency quantified by single-molecule RNA FISH and stochastic modelling.

    abstract::The human T cell leukemia virus HTLV-1 establishes a persistent infection in vivo in which the viral sense-strand transcription is usually silent at a given time in each cell. However, cellular stress responses trigger the reactivation of HTLV-1, enabling the virus to transmit to a new host cell. Using single-molecule...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008164

    authors: Miura M,Dey S,Ramanayake S,Singh A,Rueda DS,Bangham CRM

    更新日期:2019-11-18 00:00:00

  • Comprehensive analysis of iron utilization by Mycobacterium tuberculosis.

    abstract::Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008337

    authors: Zhang L,Hendrickson RC,Meikle V,Lefkowitz EJ,Ioerger TR,Niederweis M

    更新日期:2020-02-18 00:00:00

  • Nucleoporin NUP153 phenylalanine-glycine motifs engage a common binding pocket within the HIV-1 capsid protein to mediate lentiviral infectivity.

    abstract::Lentiviruses can infect non-dividing cells, and various cellular transport proteins provide crucial functions for lentiviral nuclear entry and integration. We previously showed that the viral capsid (CA) protein mediated the dependency on cellular nucleoporin (NUP) 153 during HIV-1 infection, and now demonstrate a dir...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003693

    authors: Matreyek KA,Yücel SS,Li X,Engelman A

    更新日期:2013-01-01 00:00:00

  • Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7.

    abstract::Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ aft...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000813

    authors: Phillips R,Svensson M,Aziz N,Maroof A,Brown N,Beattie L,Signoret N,Kaye PM

    更新日期:2010-03-12 00:00:00