Brucella modulates secretory trafficking via multiple type IV secretion effector proteins.

Abstract:

:The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using β-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Myeni S,Child R,Ng TW,Kupko JJ 3rd,Wehrly TD,Porcella SF,Knodler LA,Celli J

doi

10.1371/journal.ppat.1003556

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

e1003556

issue

8

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-13-00802

journal_volume

9

pub_type

杂志文章
  • A Trypanosomatid Iron Transporter that Regulates Mitochondrial Function Is Required for Leishmania amazonensis Virulence.

    abstract::Iron, an essential co-factor of respiratory chain proteins, is critical for mitochondrial function and maintenance of its redox balance. We previously reported a role for iron uptake in differentiation of Leishmania amazonensis into virulent amastigotes, by a mechanism that involves reactive oxygen species (ROS) produ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005340

    authors: Mittra B,Laranjeira-Silva MF,Perrone Bezerra de Menezes J,Jensen J,Michailowsky V,Andrews NW

    更新日期:2016-01-07 00:00:00

  • HIV-1 adaptation studies reveal a novel Env-mediated homeostasis mechanism for evading lethal hypermutation by APOBEC3G.

    abstract::HIV-1 replication normally requires Vif-mediated neutralization of APOBEC3 antiviral enzymes. Viruses lacking Vif succumb to deamination-dependent and -independent restriction processes. Here, HIV-1 adaptation studies were leveraged to ask whether viruses with an irreparable vif deletion could develop resistance to re...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007010

    authors: Ikeda T,Symeonides M,Albin JS,Li M,Thali M,Harris RS

    更新日期:2018-04-20 00:00:00

  • The Activation of Phytophthora Effector Avr3b by Plant Cyclophilin is Required for the Nudix Hydrolase Activity of Avr3b.

    abstract::Plant pathogens secrete an arsenal of effector proteins to impair host immunity. Some effectors possess enzymatic activities that can modify their host targets. Previously, we demonstrated that a Phytophthora sojae RXLR effector Avr3b acts as a Nudix hydrolase when expressed in planta; and this enzymatic activity is r...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005139

    authors: Kong G,Zhao Y,Jing M,Huang J,Yang J,Xia Y,Kong L,Ye W,Xiong Q,Qiao Y,Dong S,Ma W,Wang Y

    更新日期:2015-08-28 00:00:00

  • Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease.

    abstract::Herpesviruses encode a characteristic serine protease with a unique fold and an active site that comprises the unusual triad Ser-His-His. The protease is essential for viral replication and as such constitutes a promising drug target. In solution, a dynamic equilibrium exists between an inactive monomeric and an activ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005045

    authors: Zühlsdorf M,Werten S,Klupp BG,Palm GJ,Mettenleiter TC,Hinrichs W

    更新日期:2015-07-10 00:00:00

  • A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions.

    abstract::Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To eluc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006096

    authors: Hagiwara D,Miura D,Shimizu K,Paul S,Ohba A,Gonoi T,Watanabe A,Kamei K,Shintani T,Moye-Rowley WS,Kawamoto S,Gomi K

    更新日期:2017-01-04 00:00:00

  • Targeted mutagenesis in a human-parasitic nematode.

    abstract::Parasitic nematodes infect over 1 billion people worldwide and cause some of the most common neglected tropical diseases. Despite their prevalence, our understanding of the biology of parasitic nematodes has been limited by the lack of tools for genetic intervention. In particular, it has not yet been possible to gene...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006675

    authors: Gang SS,Castelletto ML,Bryant AS,Yang E,Mancuso N,Lopez JB,Pellegrini M,Hallem EA

    更新日期:2017-10-10 00:00:00

  • Overcoming antigenic diversity by enhancing the immunogenicity of conserved epitopes on the malaria vaccine candidate apical membrane antigen-1.

    abstract::Malaria vaccine candidate Apical Membrane Antigen-1 (AMA1) induces protection, but only against parasite strains that are closely related to the vaccine. Overcoming the AMA1 diversity problem will require an understanding of the structural basis of cross-strain invasion inhibition. A vaccine containing four diverse al...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003840

    authors: Dutta S,Dlugosz LS,Drew DR,Ge X,Ababacar D,Rovira YI,Moch JK,Shi M,Long CA,Foley M,Beeson JG,Anders RF,Miura K,Haynes JD,Batchelor AH

    更新日期:2013-01-01 00:00:00

  • TLR4 abrogates the Th1 immune response through IRF1 and IFN-β to prevent immunopathology during L. infantum infection.

    abstract::A striking feature of human visceral leishmaniasis (VL) is chronic inflammation in the spleen and liver, and VL patients present increased production levels of multiple inflammatory mediators, which contribute to tissue damage and disease severity. Here, we combined an experimental model with the transcriptional profi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008435

    authors: Sacramento LA,Benevides L,Maruyama SR,Tavares L,Fukutani KF,Francozo M,Sparwasser T,Cunha FQ,Almeida RP,da Silva JS,Carregaro V

    更新日期:2020-03-25 00:00:00

  • Secretory proteins are delivered to the septin-organized penetration interface during root infection by Verticillium dahliae.

    abstract::Successful infection of the host requires secretion of effector proteins to evade or suppress plant immunity. Secretion of effectors in root-infecting fungal pathogens, however, remains unexplored. We previously reported that Verticillium dahliae, a root-infecting phytopathogenic fungus, develops a penetration peg fro...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006275

    authors: Zhou TT,Zhao YL,Guo HS

    更新日期:2017-03-10 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

  • 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

  • Correction: HTLV-1 bZIP Factor Enhances T-cell Proliferation by Impeding the Suppressive Signaling of Co-inhibitory Receptors.

    abstract::[This corrects the article DOI: 10.1371/journal.ppat.1006120.]. ...

    journal_title:PLoS pathogens

    pub_type: 已发布勘误

    doi:10.1371/journal.ppat.1006228

    authors: Kinosada H,Yasunaga JI,Shimura K,Miyazato P,Onishi C,Iyoda T,Inaba K,Matsuoka M

    更新日期:2017-02-23 00:00:00

  • Early primed KLRG1- CMV-specific T cells determine the size of the inflationary T cell pool.

    abstract::Memory T cell inflation is a process in which a subset of cytomegalovirus (CMV) specific CD8 T cells continuously expands mainly during latent infection and establishes a large and stable population of effector memory cells in peripheral tissues. Here we set out to identify in vivo parameters that promote and limit CD...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007785

    authors: Baumann NS,Welten SPM,Torti N,Pallmer K,Borsa M,Barnstorf I,Oduro JD,Cicin-Sain L,Oxenius A

    更新日期:2019-05-13 00:00:00

  • The Staphylococcus aureus RNome and its commitment to virulence.

    abstract::Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of ba...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,评审

    doi:10.1371/journal.ppat.1002006

    authors: Felden B,Vandenesch F,Bouloc P,Romby P

    更新日期:2011-03-01 00:00:00

  • KSHV G-protein coupled receptor vGPCR oncogenic signaling upregulation of Cyclooxygenase-2 expression mediates angiogenesis and tumorigenesis in Kaposi's sarcoma.

    abstract::Kaposi's sarcoma-associated herpesvirus (KSHV) vGPCR is a constitutively active G protein-coupled receptor that subverts proliferative and inflammatory signaling pathways to induce cell transformation in Kaposi's sarcoma. Cyclooxygenase-2 (COX-2) is an inflammatory mediator that plays a key regulatory role in the acti...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009006

    authors: Medina MV,D Agostino A,Ma Q,Eroles P,Cavallin L,Chiozzini C,Sapochnik D,Cymeryng C,Hyjek E,Cesarman E,Naipauer J,Mesri EA,Coso OA

    更新日期:2020-10-15 00:00:00

  • The HSV-1 exonuclease, UL12, stimulates recombination by a single strand annealing mechanism.

    abstract::Production of concatemeric DNA is an essential step during HSV infection, as the packaging machinery must recognize longer-than-unit-length concatemers; however, the mechanism by which they are formed is poorly understood. Although it has been proposed that the viral genome circularizes and rolling circle replication ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002862

    authors: Schumacher AJ,Mohni KN,Kan Y,Hendrickson EA,Stark JM,Weller SK

    更新日期:2012-01-01 00:00:00

  • Direct identification of the Meloidogyne incognita secretome reveals proteins with host cell reprogramming potential.

    abstract::The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000192

    authors: Bellafiore S,Shen Z,Rosso MN,Abad P,Shih P,Briggs SP

    更新日期:2008-10-01 00:00:00

  • HCMV-infected cells maintain efficient nucleotide excision repair of the viral genome while abrogating repair of the host genome.

    abstract::Many viruses subvert the host cell's ability to mount and complete various DNA damage responses (DDRs) after infection. HCMV infection of permissive fibroblasts activates host DDRs at the time of viral deposition and during replication, but the DDRs remain uncompleted without arrest or apoptosis. We believe this was i...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003038

    authors: O'Dowd JM,Zavala AG,Brown CJ,Mori T,Fortunato EA

    更新日期:2012-01-01 00:00:00

  • Candida albicans white and opaque cells undergo distinct programs of filamentous growth.

    abstract::The ability to switch between yeast and filamentous forms is central to Candida albicans biology. The yeast-hyphal transition is implicated in adherence, tissue invasion, biofilm formation, phagocyte escape, and pathogenesis. A second form of morphological plasticity in C. albicans involves epigenetic switching betwee...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003210

    authors: Si H,Hernday AD,Hirakawa MP,Johnson AD,Bennett RJ

    更新日期:2013-03-01 00:00:00

  • Type I interferon programs innate myeloid dynamics and gene expression in the virally infected nervous system.

    abstract::Viral infections of central nervous system (CNS) often trigger inflammatory responses that give rise to a wide range of pathological outcomes. The CNS is equipped with an elaborate network of innate immune sentinels (e.g. microglia, macrophages, dendritic cells) that routinely serve as first responders to these infect...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003395

    authors: Nayak D,Johnson KR,Heydari S,Roth TL,Zinselmeyer BH,McGavern DB

    更新日期:2013-01-01 00:00:00

  • Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.

    abstract::Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003522

    authors: Nagaraj VA,Sundaram B,Varadarajan NM,Subramani PA,Kalappa DM,Ghosh SK,Padmanaban G

    更新日期:2013-01-01 00:00:00

  • Endopeptidase-mediated beta lactam tolerance.

    abstract::In many bacteria, inhibition of cell wall synthesis leads to cell death and lysis. The pathways and enzymes that mediate cell lysis after exposure to cell wall-acting antibiotics (e.g. beta lactams) are incompletely understood, but the activities of enzymes that degrade the cell wall ('autolysins') are thought to be c...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004850

    authors: Dörr T,Davis BM,Waldor MK

    更新日期:2015-04-17 00:00:00

  • Peli1 signaling blockade attenuates congenital zika syndrome.

    abstract::Zika virus (ZIKV) infects pregnant women and causes devastating congenital zika syndrome (CZS). How the virus is vertically transmitted to the fetus and induces neuronal loss remains unclear. We previously reported that Pellino (Peli)1, an E3 ubiquitin ligase, promotes p38MAPK activation in microglia and induction of ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008538

    authors: Luo H,Li G,Wang B,Tian B,Gao J,Zou J,Shi S,Zhu S,Peng BH,Adam A,Martinez A,Hein K,Winkelmann ER,Mahmoud Y,Zhou X,Shan C,Rossi S,Weaver S,Barrett ADT,Sun SC,Zhang W,Shi PY,Wu P,Wang T

    更新日期:2020-06-16 00:00:00

  • Inflammasome-Independent NLRP3 Restriction of a Protective Early Neutrophil Response to Pulmonary Tularemia.

    abstract::Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft chall...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006059

    authors: Periasamy S,Le HT,Duffy EB,Chin H,Harton JA

    更新日期:2016-12-07 00:00:00

  • Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation.

    abstract::In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK), key players in neuritogenesis, to prion d...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005073

    authors: Alleaume-Butaux A,Nicot S,Pietri M,Baudry A,Dakowski C,Tixador P,Ardila-Osorio H,Haeberlé AM,Bailly Y,Peyrin JM,Launay JM,Kellermann O,Schneider B

    更新日期:2015-08-04 00:00:00

  • A Novel Virus Causes Scale Drop Disease in Lates calcarifer.

    abstract::From 1992 onwards, outbreaks of a previously unknown illness have been reported in Asian seabass (Lates calcarifer) kept in maricultures in Southeast Asia. The most striking symptom of this emerging disease is the loss of scales. It was referred to as scale drop syndrome, but the etiology remained enigmatic. By using ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005074

    authors: de Groof A,Guelen L,Deijs M,van der Wal Y,Miyata M,Ng KS,van Grinsven L,Simmelink B,Biermann Y,Grisez L,van Lent J,de Ronde A,Chang SF,Schrier C,van der Hoek L

    更新日期:2015-08-07 00:00:00

  • Correction: Poxviruses: Slipping and sliding through transcription and translation.

    abstract::[This corrects the article DOI: 10.1371/journal.ppat.1006634.]. ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,已发布勘误

    doi:10.1371/journal.ppat.1006832

    authors: Walsh D

    更新日期:2018-01-04 00:00:00

  • Chromatin maturation of the HIV-1 provirus in primary resting CD4+ T cells.

    abstract::Human immunodeficiency virus type 1 (HIV-1) infection is a chronic condition, where viral DNA integrates into the genome. Latently infected cells form a persistent, heterogeneous reservoir that at any time can reactivate the integrated HIV-1. Here we confirmed that latently infected cells from HIV-1 positive study par...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008264

    authors: Lindqvist B,Svensson Akusjärvi S,Sönnerborg A,Dimitriou M,Svensson JP

    更新日期:2020-01-30 00:00:00

  • HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

    abstract::Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005111

    authors: Erdmann N,Du VY,Carlson J,Schaefer M,Jureka A,Sterrett S,Yue L,Dilernia D,Lakhi S,Tang J,Sidney J,Gilmour J,Allen S,Hunter E,Heath S,Bansal A,Goepfert PA

    更新日期:2015-08-24 00:00:00

  • TGF-beta signaling controls embryo development in the parasitic flatworm Schistosoma mansoni.

    abstract::Over 200 million people have, and another 600 million are at risk of contracting, schistosomiasis, one of the major neglected tropical diseases. Transmission of this infection, which is caused by helminth parasites of the genus Schistosoma, depends upon the release of parasite eggs from the human host. However, approx...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030052

    authors: Freitas TC,Jung E,Pearce EJ

    更新日期:2007-04-01 00:00:00