A novel secretion pathway of Salmonella enterica acts as an antivirulence modulator during salmonellosis.

Abstract:

:Salmonella spp. are Gram-negative enteropathogenic bacteria that infect a variety of vertebrate hosts. Like any other living organism, protein secretion is a fundamental process essential for various aspects of Salmonella biology. Herein we report the identification and characterization of a horizontally acquired, autonomous and previously unreported secretion pathway. In Salmonella enterica serovar Typhimurium, this novel secretion pathway is encoded by STM1669 and STM1668, designated zirT and zirS, respectively. We show that ZirT is localized to the bacterial outer membrane, expected to adopt a compact beta-barrel conformation, and functions as a translocator for ZirS. ZirS is an exoprotein, which is secreted into the extracellular environment in a ZirT-dependent manner. The ZirTS secretion pathway was found to share several important features with two-partner secretion (TPS) systems and members of the intimin/invasin family of adhesions. We show that zirTS expression is affected by zinc; and that in vivo, induction of zirT occurs distinctively in Salmonella colonizing the small intestine, but not in systemic sites. Additionally, strong expression of zirT takes place in Salmonella shed in fecal pellets during acute and persistent infections of mice. Inactivation of ZirTS results in a hypervirulence phenotype of Salmonella during oral infection of mice. Cumulatively, these results indicate that the ZirTS pathway plays a unique role as an antivirulence modulator during systemic disease and is involved in fine-tuning a host-pathogen balance during salmonellosis.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Gal-Mor O,Gibson DL,Baluta D,Vallance BA,Finlay BB

doi

10.1371/journal.ppat.1000036

subject

Has Abstract

pub_date

2008-04-04 00:00:00

pages

e1000036

issue

4

eissn

1553-7366

issn

1553-7374

journal_volume

4

pub_type

杂志文章
  • Transmission pathways of foot-and-mouth disease virus in the United Kingdom in 2007.

    abstract::Foot-and-mouth disease (FMD) virus causes an acute vesicular disease of domesticated and wild ruminants and pigs. Identifying sources of FMD outbreaks is often confounded by incomplete epidemiological evidence and the numerous routes by which virus can spread (movements of infected animals or their products, contamina...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000050

    authors: Cottam EM,Wadsworth J,Shaw AE,Rowlands RJ,Goatley L,Maan S,Maan NS,Mertens PP,Ebert K,Li Y,Ryan ED,Juleff N,Ferris NP,Wilesmith JW,Haydon DT,King DP,Paton DJ,Knowles NJ

    更新日期:2008-04-18 00:00:00

  • High-efficiency targeted editing of large viral genomes by RNA-guided nucleases.

    abstract::A facile and efficient method for the precise editing of large viral genomes is required for the selection of attenuated vaccine strains and the construction of gene therapy vectors. The type II prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)) RNA-guided nucl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004090

    authors: Bi Y,Sun L,Gao D,Ding C,Li Z,Li Y,Cun W,Li Q

    更新日期:2014-05-01 00:00:00

  • The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes.

    abstract::All pathogenesis and death associated with Plasmodium falciparum malaria is due to parasite-infected erythrocytes. Invasion of erythrocytes by P. falciparum merozoites requires specific interactions between host receptors and parasite ligands that are localized in apical organelles called micronemes. Here, we identify...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004520

    authors: Dawn A,Singh S,More KR,Siddiqui FA,Pachikara N,Ramdani G,Langsley G,Chitnis CE

    更新日期:2014-12-18 00:00:00

  • Chronic schistosomiasis suppresses HIV-specific responses to DNA-MVA and MVA-gp140 Env vaccine regimens despite antihelminthic treatment and increases helminth-associated pathology in a mouse model.

    abstract::Future HIV vaccines are expected to induce effective Th1 cell-mediated and Env-specific antibody responses that are necessary to offer protective immunity to HIV infection. However, HIV infections are highly prevalent in helminth endemic areas. Helminth infections induce polarised Th2 responses that may impair HIV vac...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007182

    authors: Dzhivhuho GA,Rehrl SA,Ndlovu H,Horsnell WGC,Brombacher F,Williamson AL,Chege GK

    更新日期:2018-07-26 00:00:00

  • A novel genetic technique in Plasmodium berghei allows liver stage analysis of genes required for mosquito stage development and demonstrates that de novo heme synthesis is essential for liver stage development in the malaria parasite.

    abstract::The combination of drug resistance, lack of an effective vaccine, and ongoing conflict and poverty means that malaria remains a major global health crisis. Understanding metabolic pathways at all parasite life stages is important in prioritising and targeting novel anti-parasitic compounds. The unusual heme synthesis ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006396

    authors: Rathnapala UL,Goodman CD,McFadden GI

    更新日期:2017-06-15 00:00:00

  • Emergence of prions selectively resistant to combination drug therapy.

    abstract::Prions are unorthodox infectious agents that replicate by templating misfolded conformations of a host-encoded glycoprotein, collectively termed PrPSc. Prion diseases are invariably fatal and currently incurable, but oral drugs that can prolong incubation times in prion-infected mice have been developed. Here, we test...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008581

    authors: Burke CM,Mark KMK,Kun J,Beauchemin KS,Supattapone S

    更新日期:2020-05-18 00:00:00

  • The effect of immune selection on the structure of the meningococcal opa protein repertoire.

    abstract::The opa genes of the Gram negative bacterium Neisseria meningitidis encode Opacity-associated outer membrane proteins whose role is to promote adhesion to the human host tissue during colonisation and invasion. Each meningococcus contains 3-4 opa loci, each of which may be occupied by one of a large number of alleles....

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000020

    authors: Callaghan MJ,Buckee CO,Jolley KA,Kriz P,Maiden MC,Gupta S

    更新日期:2008-03-14 00:00:00

  • Possibility for reverse zoonotic transmission of SARS-CoV-2 to free-ranging wildlife: A case study of bats.

    abstract::The COVID-19 pandemic highlights the substantial public health, economic, and societal consequences of virus spillover from a wildlife reservoir. Widespread human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also presents a new set of challenges when considering viral spillover from peo...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,评审

    doi:10.1371/journal.ppat.1008758

    authors: Olival KJ,Cryan PM,Amman BR,Baric RS,Blehert DS,Brook CE,Calisher CH,Castle KT,Coleman JTH,Daszak P,Epstein JH,Field H,Frick WF,Gilbert AT,Hayman DTS,Ip HS,Karesh WB,Johnson CK,Kading RC,Kingston T,Lorch JM,Mend

    更新日期:2020-09-03 00:00:00

  • ATG5 is essential for ATG8-dependent autophagy and mitochondrial homeostasis in Leishmania major.

    abstract::Macroautophagy has been shown to be important for the cellular remodelling required for Leishmania differentiation. We now demonstrate that L. major contains a functional ATG12-ATG5 conjugation system, which is required for ATG8-dependent autophagosome formation. Nascent autophagosomes were found commonly associated w...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002695

    authors: Williams RA,Smith TK,Cull B,Mottram JC,Coombs GH

    更新日期:2012-01-01 00:00:00

  • Dynamics and regulation of nuclear import and nuclear movements of HIV-1 complexes.

    abstract::The dynamics and regulation of HIV-1 nuclear import and its intranuclear movements after import have not been studied. To elucidate these essential HIV-1 post-entry events, we labeled viral complexes with two fluorescently tagged virion-incorporated proteins (APOBEC3F or integrase), and analyzed the HIV-1 dynamics of ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006570

    authors: Burdick RC,Delviks-Frankenberry KA,Chen J,Janaka SK,Sastri J,Hu WS,Pathak VK

    更新日期:2017-08-21 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

  • NEDD4 family ubiquitin ligases associate with LCMV Z's PPXY domain and are required for virus budding, but not via direct ubiquitination of Z.

    abstract::Viral late domains are used by many viruses to recruit the cellular endosomal sorting complex required for transport (ESCRT) to mediate membrane scission during viral budding. Unlike the P(S/T)AP and YPX(1-3)L late domains, which interact directly with the ESCRT proteins Tsg101 and ALIX, the molecular linkage connecti...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008100

    authors: Ziegler CM,Dang L,Eisenhauer P,Kelly JA,King BR,Klaus JP,Manuelyan I,Mattice EB,Shirley DJ,Weir ME,Bruce EA,Ballif BA,Botten J

    更新日期:2019-11-11 00:00:00

  • A live auxotrophic vaccine confers mucosal immunity and protection against lethal pneumonia caused by Pseudomonas aeruginosa.

    abstract::Pseudomonas aeruginosa is one of the leading causes of nosocomial pneumonia and its associated mortality. Moreover, extensively drug-resistant high-risk clones are globally widespread, presenting a major challenge to the healthcare systems. Despite this, no vaccine is available against this high-concerning pathogen. H...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008311

    authors: Cabral MP,Correia A,Vilanova M,Gärtner F,Moscoso M,García P,Vallejo JA,Pérez A,Francisco-Tomé M,Fuentes-Valverde V,Bou G

    更新日期:2020-02-10 00:00:00

  • Gain-of-sensitivity mutations in a Trim5-resistant primary isolate of pathogenic SIV identify two independent conserved determinants of Trim5α specificity.

    abstract::Retroviral capsid recognition by Trim5 blocks productive infection. Rhesus macaques harbor three functionally distinct Trim5 alleles: Trim5α(Q) , Trim5α(TFP) and Trim5(CypA) . Despite the high degree of amino acid identity between Trim5α(Q) and Trim5α(TFP) alleles, the Q/TFP polymorphism results in the differential re...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003352

    authors: McCarthy KR,Schmidt AG,Kirmaier A,Wyand AL,Newman RM,Johnson WE

    更新日期:2013-05-01 00:00:00

  • Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection.

    abstract::Dynamic regulation of leukocyte population size and activation state is crucial for an effective immune response. In malaria, Plasmodium parasites elicit robust host expansion of macrophages and monocytes, but the underlying mechanisms remain unclear. Here we show that myeloid expansion during P. chabaudi infection is...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006046

    authors: Fontana MF,de Melo GL,Anidi C,Hamburger R,Kim CY,Lee SY,Pham J,Kim CC

    更新日期:2016-12-06 00:00:00

  • The KdpD/KdpE two-component system: integrating K⁺ homeostasis and virulence.

    abstract::The two-component system (TCS) KdpD/KdpE, extensively studied for its regulatory role in potassium (K(+)) transport, has more recently been identified as an adaptive regulator involved in the virulence and intracellular survival of pathogenic bacteria, including Staphylococcus aureus, entero-haemorrhagic Escherichia c...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003201

    authors: Freeman ZN,Dorus S,Waterfield NR

    更新日期:2013-03-01 00:00:00

  • Inflammation fuels colicin Ib-dependent competition of Salmonella serovar Typhimurium and E. coli in enterobacterial blooms.

    abstract::The host's immune system plays a key role in modulating growth of pathogens and the intestinal microbiota in the gut. In particular, inflammatory bowel disorders and pathogen infections induce shifts of the resident commensal microbiota which can result in overgrowth of Enterobacteriaceae ("inflammation-inflicted bloo...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003844

    authors: Nedialkova LP,Denzler R,Koeppel MB,Diehl M,Ring D,Wille T,Gerlach RG,Stecher B

    更新日期:2014-01-01 00:00:00

  • Thy1+ NK [corrected] cells from vaccinia virus-primed mice confer protection against vaccinia virus challenge in the absence of adaptive lymphocytes.

    abstract::While immunological memory has long been considered the province of T- and B-lymphocytes, it has recently been reported that innate cell populations are capable of mediating memory responses. We now show that an innate memory immune response is generated in mice following infection with vaccinia virus, a poxvirus for ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002141

    authors: Gillard GO,Bivas-Benita M,Hovav AH,Grandpre LE,Panas MW,Seaman MS,Haynes BF,Letvin NL

    更新日期:2011-08-01 00:00:00

  • Exclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection.

    abstract::The whipworm Trichuris trichiura is a soil-transmitted helminth that dwells in the epithelium of the caecum and proximal colon of their hosts causing the human disease, trichuriasis. Trichuriasis is characterized by colitis attributed to the inflammatory response elicited by the parasite while tunnelling through intes...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007265

    authors: Duque-Correa MA,Karp NA,McCarthy C,Forman S,Goulding D,Sankaranarayanan G,Jenkins TP,Reid AJ,Cambridge EL,Ballesteros Reviriego C,Sanger Mouse Genetics Project.,3i consortium.,Müller W,Cantacessi C,Dougan G,Grencis RK,Ber

    更新日期:2019-01-14 00:00:00

  • Prion protein amino acid determinants of differential susceptibility and molecular feature of prion strains in mice and voles.

    abstract::The bank vole is a rodent susceptible to different prion strains from humans and various animal species. We analyzed the transmission features of different prions in a panel of seven rodent species which showed various degrees of phylogenetic affinity and specific prion protein (PrP) sequence divergences in order to i...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000113

    authors: Agrimi U,Nonno R,Dell'Omo G,Di Bari MA,Conte M,Chiappini B,Esposito E,Di Guardo G,Windl O,Vaccari G,Lipp HP

    更新日期:2008-07-25 00:00:00

  • A cardinal role for cathepsin d in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci.

    abstract::The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pat...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001262

    authors: Bewley MA,Marriott HM,Tulone C,Francis SE,Mitchell TJ,Read RC,Chain B,Kroemer G,Whyte MK,Dockrell DH

    更新日期:2011-01-27 00:00:00

  • Proteome-wide analysis of CD8+ T cell responses to EBV reveals differences between primary and persistent infection.

    abstract::Human herpesviruses are antigenically rich agents that induce strong CD8+T cell responses in primary infection yet persist for life, continually challenging T cell memory through recurrent lytic replication and potentially influencing the spectrum of antigen-specific responses. Here we describe the first lytic proteom...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007110

    authors: Forrest C,Hislop AD,Rickinson AB,Zuo J

    更新日期:2018-09-24 00:00:00

  • Selective recruitment of nuclear factors to productively replicating herpes simplex virus genomes.

    abstract::Much of the HSV-1 life cycle is carried out in the cell nucleus, including the expression, replication, repair, and packaging of viral genomes. Viral proteins, as well as cellular factors, play essential roles in these processes. Isolation of proteins on nascent DNA (iPOND) was developed to label and purify cellular r...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004939

    authors: Dembowski JA,DeLuca NA

    更新日期:2015-05-27 00:00:00

  • Role of SpaO in the assembly of the sorting platform of a Salmonella type III secretion system.

    abstract::Many bacterial pathogens and symbionts use type III secretion machines to interact with their hosts by injecting bacterial effector proteins into host target cells. A central component of this complex machine is the cytoplasmic sorting platform, which orchestrates the engagement and preparation of type III secreted pr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007565

    authors: Lara-Tejero M,Qin Z,Hu B,Butan C,Liu J,Galán JE

    更新日期:2019-01-22 00:00:00

  • L-glutamine Induces Expression of Listeria monocytogenes Virulence Genes.

    abstract::The high environmental adaptability of bacteria is contingent upon their ability to sense changes in their surroundings. Bacterial pathogen entry into host poses an abrupt and dramatic environmental change, during which successful pathogens gauge multiple parameters that signal host localization. The facultative human...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006161

    authors: Haber A,Friedman S,Lobel L,Burg-Golani T,Sigal N,Rose J,Livnat-Levanon N,Lewinson O,Herskovits AA

    更新日期:2017-01-23 00:00:00

  • VE-cadherin cleavage by LasB protease from Pseudomonas aeruginosa facilitates type III secretion system toxicity in endothelial cells.

    abstract::Infection of the vascular system by Pseudomonas aeruginosa (Pa) occurs during bacterial dissemination in the body or in blood-borne infections. Type 3 secretion system (T3SS) toxins from Pa induce a massive retraction when injected into endothelial cells. Here, we addressed the role of type 2 secretion system (T2SS) e...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003939

    authors: Golovkine G,Faudry E,Bouillot S,Voulhoux R,Attrée I,Huber P

    更新日期:2014-03-13 00:00:00

  • Phenylbutyrate Is Bacteriostatic against Mycobacterium tuberculosis and Regulates the Macrophage Response to Infection, Synergistically with 25-Hydroxy-Vitamin D3.

    abstract::Adjunctive vitamin D treatment for pulmonary tuberculosis enhances resolution of inflammation but has modest effects on bacterial clearance. Sodium 4-phenylbutyrate (PBA) is in clinical use for a range of conditions and has been shown to synergise with vitamin D metabolites to upregulate cathelicidin antimicrobial pep...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005007

    authors: Coussens AK,Wilkinson RJ,Martineau AR

    更新日期:2015-07-02 00:00:00

  • Agr-mediated dispersal of Staphylococcus aureus biofilms.

    abstract::The agr quorum-sensing system of Staphylococcus aureus modulates the expression of virulence factors in response to autoinducing peptides (AIPs). Recent studies have suggested a role for the agr system in S. aureus biofilm development, as agr mutants exhibit a high propensity to form biofilms, and cells dispersing fro...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000052

    authors: Boles BR,Horswill AR

    更新日期:2008-04-25 00:00:00

  • The HIV-1 envelope transmembrane domain binds TLR2 through a distinct dimerization motif and inhibits TLR2-mediated responses.

    abstract::HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR) responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TM...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004248

    authors: Reuven EM,Ali M,Rotem E,Schwarzer R,Gramatica A,Futerman AH,Shai Y

    更新日期:2014-08-14 00:00:00

  • Titan cells formation in Cryptococcus neoformans is finely tuned by environmental conditions and modulated by positive and negative genetic regulators.

    abstract::The pathogenic fungus Cryptococcus neoformans exhibits morphological changes in cell size during lung infection, producing both typical size 5 to 7 μm cells and large titan cells (> 10 μm and up to 100 μm). We found and optimized in vitro conditions that produce titan cells in order to identify the ancestry of titan c...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006982

    authors: Hommel B,Mukaremera L,Cordero RJB,Coelho C,Desjardins CA,Sturny-Leclère A,Janbon G,Perfect JR,Fraser JA,Casadevall A,Cuomo CA,Dromer F,Nielsen K,Alanio A

    更新日期:2018-05-18 00:00:00