Differential Impacts on Host Transcription by ROP and GRA Effectors from the Intracellular Parasite Toxoplasma gondii.

Abstract:

:The intracellular parasite Toxoplasma gondii employs a vast array of effector proteins from the rhoptry and dense granule organelles to modulate host cell biology; these effectors are known as ROPs and GRAs, respectively. To examine the individual impacts of ROPs and GRAs on host gene expression, we developed a robust, novel protocol to enrich for ultrapure populations of a naturally occurring and reproducible population of host cells called uninfected-injected (U-I) cells, which Toxoplasma injects with ROPs but subsequently fails to invade. We then performed single-cell transcriptomic analysis at 1 to 3 h postinfection on U-I cells (as well as on uninfected and infected controls) arising from infection with either wild-type parasites or parasites lacking the MYR1 protein, which is required for soluble GRAs to cross the parasitophorous vacuole membrane (PVM) and reach the host cell cytosol. Based on comparisons of infected and U-I cells, the host's earliest response to infection appears to be driven primarily by the injected ROPs, which appear to induce immune and cellular stress pathways. These ROP-dependent proinflammatory signatures appear to be counteracted by at least some of the MYR1-dependent GRAs and may be enhanced by the MYR-independent GRAs (which are found embedded within the PVM). Finally, signatures detected in uninfected bystander cells from the infected monolayers suggest that MYR1-dependent paracrine effects also counteract inflammatory ROP-dependent processes.IMPORTANCE This work performs transcriptomic analysis of U-I cells, captures the earliest stage of a host cell's interaction with Toxoplasma gondii, and dissects the effects of individual classes of parasite effectors on host cell biology.

journal_name

mBio

journal_title

mBio

authors

Rastogi S,Xue Y,Quake SR,Boothroyd JC

doi

10.1128/mBio.00182-20

subject

Has Abstract

pub_date

2020-06-09 00:00:00

issue

3

issn

2150-7511

pii

mBio.00182-20

journal_volume

11

pub_type

杂志文章

相关文献

mBio文献大全
  • Structural and mechanistic roles of novel chemical ligands on the SdiA quorum-sensing transcription regulator.

    abstract:UNLABELLED:Bacteria engage in chemical signaling, termed quorum sensing (QS), to mediate intercellular communication, mimicking multicellular organisms. The LuxR family of QS transcription factors regulates gene expression, coordinating population behavior by sensing endogenous acyl homoserine lactones (AHLs). However,...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02429-14

    authors: Nguyen Y,Nguyen NX,Rogers JL,Liao J,MacMillan JB,Jiang Y,Sperandio V

    更新日期:2015-03-31 00:00:00

  • Uninfected Bystander Cells Impact the Measurement of HIV-Specific Antibody-Dependent Cellular Cytotoxicity Responses.

    abstract::The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus co...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00358-18

    authors: Richard J,Prévost J,Baxter AE,von Bredow B,Ding S,Medjahed H,Delgado GG,Brassard N,Stürzel CM,Kirchhoff F,Hahn BH,Parsons MS,Kaufmann DE,Evans DT,Finzi A

    更新日期:2018-03-20 00:00:00

  • In Situ Molecular Architecture of the Helicobacter pylori Cag Type IV Secretion System.

    abstract::Helicobacter pylori colonizes about half of humans worldwide, and its presence in the gastric mucosa is associated with an increased risk of gastric adenocarcinoma, gastric lymphoma, and peptic ulcer disease. H. pylori strains carrying the cag pathogenicity island (cagPAI) are associated with increased risk of disease...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00849-19

    authors: Hu B,Khara P,Song L,Lin AS,Frick-Cheng AE,Harvey ML,Cover TL,Christie PJ

    更新日期:2019-05-14 00:00:00

  • Mycobacterium tuberculosis alters the metalloprotease activity of the COP9 signalosome.

    abstract::Inhibition of apoptotic death of macrophages by Mycobacterium tuberculosis represents an important mechanism of virulence that results in pathogen survival both in vitro and in vivo. To identify M. tuberculosis virulence determinants involved in the modulation of apoptosis, we previously screened a transposon bank of ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01278-14

    authors: Danelishvili L,Babrak L,Rose SJ,Everman J,Bermudez LE

    更新日期:2014-08-19 00:00:00

  • Sur7 promotes plasma membrane organization and is needed for resistance to stressful conditions and to the invasive growth and virulence of Candida albicans.

    abstract::The human fungal pathogen Candida albicans causes lethal systemic infections because of its ability to grow and disseminate in a host. The C. albicans plasma membrane is essential for virulence by acting as a protective barrier and through its key roles in interfacing with the environment, secretion of virulence facto...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00254-11

    authors: Douglas LM,Wang HX,Keppler-Ross S,Dean N,Konopka JB

    更新日期:2011-12-27 00:00:00

  • Analysis of the Protein Kinase A-Regulated Proteome of Cryptococcus neoformans Identifies a Role for the Ubiquitin-Proteasome Pathway in Capsule Formation.

    abstract:UNLABELLED:The opportunistic fungal pathogen Cryptococcus neoformans causes life-threatening meningitis in immunocompromised individuals. The expression of virulence factors, including capsule and melanin, is in part regulated by the cyclic-AMP/protein kinase A (cAMP/PKA) signal transduction pathway. In this study, we ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01862-15

    authors: Geddes JM,Caza M,Croll D,Stoynov N,Foster LJ,Kronstad JW

    更新日期:2016-01-12 00:00:00

  • Convergent bacterial microbiotas in the fungal agricultural systems of insects.

    abstract:UNLABELLED:The ability to cultivate food is an innovation that has produced some of the most successful ecological strategies on the planet. Although most well recognized in humans, where agriculture represents a defining feature of civilization, species of ants, beetles, and termites have also independently evolved sy...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02077-14

    authors: Aylward FO,Suen G,Biedermann PH,Adams AS,Scott JJ,Malfatti SA,Glavina del Rio T,Tringe SG,Poulsen M,Raffa KF,Klepzig KD,Currie CR

    更新日期:2014-11-18 00:00:00

  • Type III secretion of ExoU is critical during early Pseudomonas aeruginosa pneumonia.

    abstract:UNLABELLED:The Pseudomonas aeruginosa type III secretion system has been associated with poor outcomes in both animal models and human patients. Despite a large number of studies exploring the regulation of type III secretion in vitro, little is known about the timing of secretion during mammalian infection. Here we de...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00032-13

    authors: Howell HA,Logan LK,Hauser AR

    更新日期:2013-03-12 00:00:00

  • The Peptidoglycan-Binding Protein SjcF1 Influences Septal Junction Function and Channel Formation in the Filamentous Cyanobacterium Anabaena.

    abstract:UNLABELLED:Filamentous, heterocyst-forming cyanobacteria exchange nutrients and regulators between cells for diazotrophic growth. Two alternative modes of exchange have been discussed involving transport either through the periplasm or through septal junctions linking adjacent cells. Septal junctions and channels in th...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00376-15

    authors: Rudolf M,Tetik N,Ramos-León F,Flinner N,Ngo G,Stevanovic M,Burnat M,Pernil R,Flores E,Schleiff E

    更新日期:2015-06-30 00:00:00

  • Septins arrange F-actin-containing fibers on the Chlamydia trachomatis inclusion and are required for normal release of the inclusion by extrusion.

    abstract::Chlamydia trachomatis is an obligate intracellular human pathogen that grows inside a membranous, cytosolic vacuole termed an inclusion. Septins are a group of 13 GTP-binding proteins that assemble into oligomeric complexes and that can form higher-order filaments. We report here that the septins SEPT2, -9, -11, and p...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01802-14

    authors: Volceanov L,Herbst K,Biniossek M,Schilling O,Haller D,Nölke T,Subbarayal P,Rudel T,Zieger B,Häcker G

    更新日期:2014-10-07 00:00:00

  • A SpoIID Homolog Cleaves Glycan Strands at the Chlamydial Division Septum.

    abstract::Chlamydiales species are obligate intracellular bacteria lacking a classical peptidoglycan sacculus but relying on peptidoglycan synthesis for cytokinesis. While septal peptidoglycan biosynthesis seems to be regulated by MreB actin and its membrane anchor RodZ rather than FtsZ tubulin in Chlamydiales, the mechanism of...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01128-19

    authors: Jacquier N,Yadav AK,Pillonel T,Viollier PH,Cava F,Greub G

    更新日期:2019-07-16 00:00:00

  • Hybrid Vibrio cholerae El Tor lacking SXT identified as the cause of a cholera outbreak in the Philippines.

    abstract:UNLABELLED:Cholera continues to be a global threat, with high rates of morbidity and mortality. In 2011, a cholera outbreak occurred in Palawan, Philippines, affecting more than 500 people, and 20 individuals died. Vibrio cholerae O1 was confirmed as the etiological agent. Source attribution is critical in cholera outb...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00047-15

    authors: Klinzing DC,Choi SY,Hasan NA,Matias RR,Tayag E,Geronimo J,Skowronski E,Rashed SM,Kawashima K,Rosenzweig CN,Gibbons HS,Torres BC,Liles V,Alfon AC,Juan ML,Natividad FF,Cebula TA,Colwell RR

    更新日期:2015-04-21 00:00:00

  • Developmental Dynamics of Long Noncoding RNA Expression during Sexual Fruiting Body Formation in Fusarium graminearum.

    abstract::Long noncoding RNA (lncRNA) plays important roles in sexual development in eukaryotes. In filamentous fungi, however, little is known about the expression and roles of lncRNAs during fruiting body formation. By profiling developmental transcriptomes during the life cycle of the plant-pathogenic fungus Fusarium gramine...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01292-18

    authors: Kim W,Miguel-Rojas C,Wang J,Townsend JP,Trail F

    更新日期:2018-08-14 00:00:00

  • Contribution of a single host genetic locus to mouse adenovirus type 1 infection and encephalitis.

    abstract:UNLABELLED:Susceptibility to mouse adenovirus type 1 (MAV-1) is mouse strain dependent; susceptible mice die from hemorrhagic encephalomyelitis. The MAV-1 susceptibility quantitative trait locus Msq1 accounts for ~40% of the phenotypic (brain viral load) variance that occurs between resistant BALB/c and susceptible SJL...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00131-12

    authors: Hsu TH,Althaus IW,Foreman O,Spindler KR

    更新日期:2012-05-29 00:00:00

  • Metabolite changes signal genetic regulatory mechanisms for robust cell behavior.

    abstract:UNLABELLED:Exploiting mechanisms of utilizing the sugar d-galactose in Escherichia coli as a model system, we explored the consequences of accumulation of critical intermediates of the d-galactose metabolic pathways by monitoring cell growth, metabolites, and transcript profiles. These studies revealed both metabolic n...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00972-13

    authors: Lee SJ,Trostel A,Adhya S

    更新日期:2014-01-28 00:00:00

  • Corynebacterium pseudodiphtheriticum Exploits Staphylococcus aureus Virulence Components in a Novel Polymicrobial Defense Strategy.

    abstract::Commensal bacteria in the human nasal cavity are known to suppress opportunistic pathogen colonization by competing for limited space and nutrients. It has become increasingly apparent that some commensal bacteria also produce toxic compounds that directly inhibit or kill incoming competitors. Numerous studies suggest...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02491-18

    authors: Hardy BL,Dickey SW,Plaut RD,Riggins DP,Stibitz S,Otto M,Merrell DS

    更新日期:2019-01-08 00:00:00

  • Evaluation of Antihemagglutinin and Antineuraminidase Antibodies as Correlates of Protection in an Influenza A/H1N1 Virus Healthy Human Challenge Model.

    abstract:UNLABELLED:Despite long-term investment, influenza continues to be a significant worldwide problem. The cornerstone of protection remains vaccination, and approved vaccines seek to elicit a hemagglutination inhibition (HAI) titer of ≥1:40 as the primary correlate of protection. However, recent poor vaccine performance ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00417-16

    authors: Memoli MJ,Shaw PA,Han A,Czajkowski L,Reed S,Athota R,Bristol T,Fargis S,Risos K,Powers JH,Davey RT Jr,Taubenberger JK

    更新日期:2016-04-19 00:00:00

  • The Yeast PCNA Unloader Elg1 RFC-Like Complex Plays a Role in Eliciting the DNA Damage Checkpoint.

    abstract::The PCNA (proliferating cell nuclear antigen) ring plays central roles during DNA replication and repair. The yeast Elg1 RFC-like complex (RLC) is the principal unloader of chromatin-bound PCNA and thus plays a central role in maintaining genome stability. Here we identify a role for Elg1 in the unloading of PCNA duri...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01159-19

    authors: Sau S,Liefshitz B,Kupiec M

    更新日期:2019-06-11 00:00:00

  • Identification of a New Lipoprotein Export Signal in Gram-Negative Bacteria.

    abstract::Bacteria of the phylum Bacteroidetes, including commensal organisms and opportunistic pathogens, harbor abundant surface-exposed multiprotein membrane complexes (Sus-like systems) involved in carbohydrate acquisition. These complexes have been mostly linked to commensalism, and in some instances, they have also been s...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01232-16

    authors: Lauber F,Cornelis GR,Renzi F

    更新日期:2016-10-25 00:00:00

  • The pause on Avian H5N1 influenza virus transmission research should be ended.

    abstract::A voluntary 60-day pause on avian H5N1 influenza virus transmission research was announced in January 2012 by the international community of influenza scientists engaged in this work to provide time to explain the benefits of such work and the risk mitigation measures in place. Subsequently, the pause was extended to ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00358-12

    authors: Fouchier RA,García-Sastre A,Kawaoka Y

    更新日期:2012-11-01 00:00:00

  • Imaging mass spectrometry reveals highly specific interactions between actinomycetes to activate specialized metabolic gene clusters.

    abstract::The genomes of actinomycetes contain numerous gene clusters potentially able to encode the production of many antibiotics and other specialized metabolites that are not expressed during growth under typical laboratory conditions. Undoubtedly, this reflects the soil habitat of these organisms, which is highly complex p...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00612-13

    authors: Hopwood DA

    更新日期:2013-09-03 00:00:00

  • The Viral Polymerase Complex Mediates the Interaction of Viral Ribonucleoprotein Complexes with Recycling Endosomes during Sendai Virus Assembly.

    abstract::Paramyxoviruses are negative-sense single-stranded RNA viruses that comprise many important human and animal pathogens, including human parainfluenza viruses. These viruses bud from the plasma membrane of infected cells after the viral ribonucleoprotein complex (vRNP) is transported from the cytoplasm to the cell memb...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02028-20

    authors: Genoyer E,Kulej K,Hung CT,Thibault PA,Azarm K,Takimoto T,Garcia BA,Lee B,Lakdawala S,Weitzman MD,López CB

    更新日期:2020-08-25 00:00:00

  • Strong In Vivo Inhibition of HIV-1 Replication by Nullbasic, a Tat Mutant.

    abstract::Nullbasic is a mutant form of the HIV-1 transcriptional activator protein (Tat) that strongly inhibits HIV-1 transcription and replication in lymphocytes in vitro To investigate Nullbasic inhibition in vivo, we employed an NSG mouse model where animals were engrafted with primary human CD4+ cells expressing a Nullbasi...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01769-19

    authors: Jin H,Sun Y,Li D,Lin MH,Lor M,Rustanti L,Harrich D

    更新日期:2019-08-27 00:00:00

  • Petrobactin Is Exported from Bacillus anthracis by the RND-Type Exporter ApeX.

    abstract::Bacillus anthracis-a Gram-positive, spore-forming bacterium-causes anthrax, a highly lethal disease with high bacteremia titers. Such rapid growth requires ample access to nutrients, including iron. However, access to this critical metal is heavily restricted in mammals, which requires B. anthracis to employ petrobact...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01238-17

    authors: Hagan AK,Tripathi A,Berger D,Sherman DH,Hanna PC

    更新日期:2017-09-12 00:00:00

  • Comparative genomics of pneumocystis species suggests the absence of genes for myo-inositol synthesis and reliance on inositol transport and metabolism.

    abstract:UNLABELLED:In the context of deciphering the metabolic strategies of the obligate pathogenic fungi in the genus Pneumocystis, the genomes of three species (P. carinii, P. murina, and P. jirovecii) were compared among themselves and with the free-living, phylogenetically related fission yeast (Schizosaccharomyces pombe)...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01834-14

    authors: Porollo A,Sesterhenn TM,Collins MS,Welge JA,Cushion MT

    更新日期:2014-11-04 00:00:00

  • Shigella sonnei O-Antigen Inhibits Internalization, Vacuole Escape, and Inflammasome Activation.

    abstract::Two Shigella species, Shigella flexneri and Shigella sonnei, cause approximately 90% of bacterial dysentery worldwide. While S. flexneri is the dominant species in low-income countries, S. sonnei causes the majority of infections in middle- and high-income countries. S. flexneri is a prototypic cytosolic bacterium; on...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02654-19

    authors: Watson JL,Sanchez-Garrido J,Goddard PJ,Torraca V,Mostowy S,Shenoy AR,Clements A

    更新日期:2019-12-17 00:00:00

  • High-resolution transcriptomic analysis of the adaptive response of Staphylococcus aureus during acute and chronic phases of osteomyelitis.

    abstract:UNLABELLED:Osteomyelitis is a difficult-to-eradicate bone infection typically caused by Staphylococcus aureus. In this study, we investigated the in vivo transcriptional adaptation of S. aureus during bone infection. To this end, we determined the transcriptome of S. aureus during the acute (day 7) and chronic (day 28)...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01775-14

    authors: Szafranska AK,Oxley AP,Chaves-Moreno D,Horst SA,Roßlenbroich S,Peters G,Goldmann O,Rohde M,Sinha B,Pieper DH,Löffler B,Jauregui R,Wos-Oxley ML,Medina E

    更新日期:2014-12-23 00:00:00

  • Novel transporter required for biogenesis of cbb3-type cytochrome c oxidase in Rhodobacter capsulatus.

    abstract:UNLABELLED:The acquisition, delivery, and incorporation of metals into their respective metalloproteins are important cellular processes. These processes are tightly controlled in order to prevent exposure of cells to free-metal concentrations that could yield oxidative damage. Copper (Cu) is one such metal that is req...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00293-11

    authors: Ekici S,Yang H,Koch HG,Daldal F

    更新日期:2012-01-31 00:00:00

  • Human claudin-8 and -14 are receptors capable of conveying the cytotoxic effects of Clostridium perfringens enterotoxin.

    abstract:UNLABELLED:Clostridium perfringens enterotoxin (CPE) contributes to several important human gastrointestinal (GI) diseases. This toxin and its derivatives are also being explored for translational applications, i.e., cancer therapy or drug delivery. Some, but not all, members of the 24-member claudin (Cldn) family of m...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00594-12

    authors: Shrestha A,McClane BA

    更新日期:2013-01-15 00:00:00

  • Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX3CR1+ Macrophages in Tissue Repair.

    abstract::Arthritogenic alphaviruses such as Ross River and Chikungunya viruses cause debilitating muscle and joint pain and pose significant challenges in the light of recent outbreaks. How host immune responses are orchestrated after alphaviral infections and lead to musculoskeletal inflammation remains poorly understood. Her...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.03353-19

    authors: Zaid A,Tharmarajah K,Mostafavi H,Freitas JR,Sheng KC,Foo SS,Chen W,Vider J,Liu X,West NP,Herrero LJ,Taylor A,Mackay LK,Getts DR,King NJC,Mahalingam S

    更新日期:2020-03-03 00:00:00