Streptococcal Lancefield polysaccharides are critical cell wall determinants for human Group IIA secreted phospholipase A2 to exert its bactericidal effects.

Abstract:

:Human Group IIA secreted phospholipase A2 (hGIIA) is an acute phase protein with bactericidal activity against Gram-positive bacteria. Infection models in hGIIA transgenic mice have suggested the importance of hGIIA as an innate defense mechanism against the human pathogens Group A Streptococcus (GAS) and Group B Streptococcus (GBS). Compared to other Gram-positive bacteria, GAS is remarkably resistant to hGIIA activity. To identify GAS resistance mechanisms, we exposed a highly saturated GAS M1 transposon library to recombinant hGIIA and compared relative mutant abundance with library input through transposon-sequencing (Tn-seq). Based on transposon prevalence in the output library, we identified nine genes, including dltA and lytR, conferring increased hGIIA susceptibility. In addition, seven genes conferred increased hGIIA resistance, which included two genes, gacH and gacI that are located within the Group A Carbohydrate (GAC) gene cluster. Using GAS 5448 wild-type and the isogenic gacI mutant and gacI-complemented strains, we demonstrate that loss of the GAC N-acetylglucosamine (GlcNAc) side chain in the ΔgacI mutant increases hGIIA resistance approximately 10-fold, a phenotype that is conserved across different GAS serotypes. Increased resistance is associated with delayed penetration of hGIIA through the cell wall. Correspondingly, loss of the Lancefield Group B Carbohydrate (GBC) rendered GBS significantly more resistant to hGIIA-mediated killing. This suggests that the streptococcal Lancefield antigens, which are critical determinants for streptococcal physiology and virulence, are required for the bactericidal enzyme hGIIA to exert its bactericidal function.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

van Hensbergen VP,Movert E,de Maat V,Lüchtenborg C,Le Breton Y,Lambeau G,Payré C,Henningham A,Nizet V,van Strijp JAG,Brügger B,Carlsson F,McIver KS,van Sorge NM

doi

10.1371/journal.ppat.1007348

subject

Has Abstract

pub_date

2018-10-15 00:00:00

pages

e1007348

issue

10

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-18-00390

journal_volume

14

pub_type

杂志文章
  • Draft genome sequencing of giardia intestinalis assemblage B isolate GS: is human giardiasis caused by two different species?

    abstract::Giardia intestinalis is a major cause of diarrheal disease worldwide and two major Giardia genotypes, assemblages A and B, infect humans. The genome of assemblage A parasite WB was recently sequenced, and the structurally compact 11.7 Mbp genome contains simplified basic cellular machineries and metabolism. We here pe...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000560

    authors: Franzén O,Jerlström-Hultqvist J,Castro E,Sherwood E,Ankarklev J,Reiner DS,Palm D,Andersson JO,Andersson B,Svärd SG

    更新日期:2009-08-01 00:00:00

  • The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi.

    abstract::The causative agent of Lyme borreliosis, the spirochete Borrelia burgdorferi, has been shown to induce expression of the urokinase receptor (uPAR); however, the role of uPAR in the immune response against Borrelia has never been investigated. uPAR not only acts as a proteinase receptor, but can also, dependently or in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000447

    authors: Hovius JW,Bijlsma MF,van der Windt GJ,Wiersinga WJ,Boukens BJ,Coumou J,Oei A,de Beer R,de Vos AF,van 't Veer C,van Dam AP,Wang P,Fikrig E,Levi MM,Roelofs JJ,van der Poll T

    更新日期:2009-05-01 00:00:00

  • Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

    abstract::In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000362

    authors: Rittner HL,Hackel D,Voigt P,Mousa S,Stolz A,Labuz D,Schäfer M,Schaefer M,Stein C,Brack A

    更新日期:2009-04-01 00:00:00

  • Mechanistic Studies and Modeling Reveal the Origin of Differential Inhibition of Gag Polymorphic Viruses by HIV-1 Maturation Inhibitors.

    abstract::HIV-1 maturation inhibitors (MIs) disrupt the final step in the HIV-1 protease-mediated cleavage of the Gag polyprotein between capsid p24 capsid (CA) and spacer peptide 1 (SP1), leading to the production of infectious virus. BMS-955176 is a second generation MI with improved antiviral activity toward polymorphic Gag ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005990

    authors: Lin Z,Cantone J,Lu H,Nowicka-Sans B,Protack T,Yuan T,Yang H,Liu Z,Drexler D,Regueiro-Ren A,Meanwell NA,Cockett M,Krystal M,Lataillade M,Dicker IB

    更新日期:2016-11-28 00:00:00

  • Genome sequence of Babesia bovis and comparative analysis of apicomplexan hemoprotozoa.

    abstract::Babesia bovis is an apicomplexan tick-transmitted pathogen of cattle imposing a global risk and severe constraints to livestock health and economic development. The complete genome sequence was undertaken to facilitate vaccine antigen discovery, and to allow for comparative analysis with the related apicomplexan hemop...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030148

    authors: Brayton KA,Lau AO,Herndon DR,Hannick L,Kappmeyer LS,Berens SJ,Bidwell SL,Brown WC,Crabtree J,Fadrosh D,Feldblum T,Forberger HA,Haas BJ,Howell JM,Khouri H,Koo H,Mann DJ,Norimine J,Paulsen IT,Radune D,Ren Q,Smith

    更新日期:2007-10-19 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

  • Sensing of cell-associated HTLV by plasmacytoid dendritic cells is regulated by dense β-galactoside glycosylation.

    abstract::Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon pr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007589

    authors: Assil S,Futsch N,Décembre E,Alais S,Gessain A,Cosset FL,Mahieux R,Dreux M,Dutartre H

    更新日期:2019-02-28 00:00:00

  • Systematic Structural Analyses of Attachment Organelle in Mycoplasma pneumoniae.

    abstract::Mycoplasma pneumoniae, a human pathogenic bacterium, glides on host cell surfaces by a unique and unknown mechanism. It forms an attachment organelle at a cell pole as a membrane protrusion composed of surface and internal structures, with a highly organized architecture. In the present study, we succeeded in isolatin...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005299

    authors: Nakane D,Kenri T,Matsuo L,Miyata M

    更新日期:2015-12-03 00:00:00

  • Near surface swimming of Salmonella Typhimurium explains target-site selection and cooperative invasion.

    abstract::Targeting of permissive entry sites is crucial for bacterial infection. The targeting mechanisms are incompletely understood. We have analyzed target-site selection by S. Typhimurium. This enteropathogenic bacterium employs adhesins (e.g. fim) and the type III secretion system 1 (TTSS-1) for host cell binding, the tri...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002810

    authors: Misselwitz B,Barrett N,Kreibich S,Vonaesch P,Andritschke D,Rout S,Weidner K,Sormaz M,Songhet P,Horvath P,Chabria M,Vogel V,Spori DM,Jenny P,Hardt WD

    更新日期:2012-01-01 00:00:00

  • PKCη/Rdx-driven phosphorylation of PDK1: a novel mechanism promoting cancer cell survival and permissiveness for parvovirus-induced lysis.

    abstract::The intrinsic oncotropism and oncosuppressive activities of rodent protoparvoviruses (PVs) are opening new prospects for cancer virotherapy. Virus propagation, cytolytic activity, and spread are tightly connected to activation of the PDK1 signaling cascade, which delays stress-induced cell death and sustains functioni...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004703

    authors: Bär S,Rommelaere J,Nüesch JP

    更新日期:2015-03-05 00:00:00

  • Clonorchis sinensis excretory-secretory products increase malignant characteristics of cholangiocarcinoma cells in three-dimensional co-culture with biliary ductal plates.

    abstract::Clonorchis sinensis is a carcinogenic human liver fluke, prolonged infection which provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma (CCA). These effects are driven by direct physical damage caused by the worms, as well as chemical irritation from their excretory-s...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007818

    authors: Won J,Cho Y,Lee D,Jeon BY,Ju JW,Chung S,Pak JH

    更新日期:2019-05-23 00:00:00

  • Attenuation of 40S ribosomal subunit abundance differentially affects host and HCV translation and suppresses HCV replication.

    abstract::For Hepatitis C virus (HCV), initiation of translation is cap-independently mediated by its internal ribosome entry site (IRES). Unlike other IRES-containing viruses that shut off host cap-dependent translation, translation of HCV coexists with that of the host. How HCV IRES-mediated translation is regulated in the in...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002766

    authors: Huang JY,Su WC,Jeng KS,Chang TH,Lai MM

    更新日期:2012-06-01 00:00:00

  • Constraints to genetic exchange support gene coadaptation in a tripartite RNA virus.

    abstract::Genetic exchange by recombination, or reassortment of genomic segments, has been shown to be an important process in RNA virus evolution, resulting often in important phenotypic changes affecting host range and virulence. However, data from numerous systems indicate that reassortant or recombinant genotypes could be s...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.0030008

    authors: Escriu F,Fraile A,García-Arenal F

    更新日期:2007-01-01 00:00:00

  • Rapid pathogen-induced apoptosis: a mechanism used by dendritic cells to limit intracellular replication of Legionella pneumophila.

    abstract::Dendritic cells (DCs) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites, and then migrate to lymphatic organs to display foreign peptides to naïve T cells. There are several examples where DCs have been shown to be more efficient at restricting the intracellular replicatio...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000478

    authors: Nogueira CV,Lindsten T,Jamieson AM,Case CL,Shin S,Thompson CB,Roy CR

    更新日期:2009-06-01 00:00:00

  • EBNA2-deleted Epstein-Barr virus (EBV) isolate, P3HR1, causes Hodgkin-like lymphomas and diffuse large B cell lymphomas with type II and Wp-restricted latency types in humanized mice.

    abstract::EBV transforms B cells in vitro and causes human B-cell lymphomas including classical Hodgkin lymphoma (CHL), Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). The EBV latency protein, EBNA2, transcriptionally activates the promoters of all latent viral protein-coding genes expressed in type III EBV lat...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008590

    authors: Li C,Romero-Masters JC,Huebner S,Ohashi M,Hayes M,Bristol JA,Nelson SE,Eichelberg MR,Van Sciver N,Ranheim EA,Scott RS,Johannsen EC,Kenney SC

    更新日期:2020-06-15 00:00:00

  • Dengue Virus Nonstructural Protein 5 (NS5) Assembles into a Dimer with a Unique Methyltransferase and Polymerase Interface.

    abstract::Flavivirus nonstructural protein 5 (NS5) consists of methyltransferase (MTase) and RNA-dependent RNA polymerase (RdRp) domains, which catalyze 5'-RNA capping/methylation and RNA synthesis, respectively, during viral genome replication. Although the crystal structure of flavivirus NS5 is known, no data about the quater...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005451

    authors: Klema VJ,Ye M,Hindupur A,Teramoto T,Gottipati K,Padmanabhan R,Choi KH

    更新日期:2016-02-19 00:00:00

  • Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli.

    abstract::Toxin-antitoxin (TA) systems are prevalent in many bacterial genomes and have been implicated in biofilm and persister cell formation, but the contribution of individual chromosomally encoded TA systems during bacterial pathogenesis is not well understood. Of the known TA systems encoded by Escherichia coli, only a su...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002954

    authors: Norton JP,Mulvey MA

    更新日期:2012-01-01 00:00:00

  • Leishmania mitochondrial peroxiredoxin plays a crucial peroxidase-unrelated role during infection: insight into its novel chaperone activity.

    abstract::Two-cysteine peroxiredoxins are ubiquitous peroxidases that play various functions in cells. In Leishmania and related trypanosomatids, which lack catalase and selenium-glutathione peroxidases, the discovery of this family of enzymes provided the molecular basis for peroxide removal in these organisms. In this report ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002325

    authors: Castro H,Teixeira F,Romao S,Santos M,Cruz T,Flórido M,Appelberg R,Oliveira P,Ferreira-da-Silva F,Tomás AM

    更新日期:2011-10-01 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

  • Horizontal versus familial transmission of Helicobacter pylori.

    abstract::Transmission of Helicobacter pylori is thought to occur mainly during childhood, and predominantly within families. However, due to the difficulty of obtaining H. pylori isolates from large population samples and to the extensive genetic diversity between isolates, the transmission and spread of H. pylori remain poorl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000180

    authors: Schwarz S,Morelli G,Kusecek B,Manica A,Balloux F,Owen RJ,Graham DY,van der Merwe S,Achtman M,Suerbaum S

    更新日期:2008-10-01 00:00:00

  • Mutations in dnaA and a cryptic interaction site increase drug resistance in Mycobacterium tuberculosis.

    abstract::Genomic dissection of antibiotic resistance in bacterial pathogens has largely focused on genetic changes conferring growth above a single critical concentration of drug. However, reduced susceptibility to antibiotics-even below this breakpoint-is associated with poor treatment outcomes in the clinic, including in tub...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009063

    authors: Hicks ND,Giffen SR,Culviner PH,Chao MC,Dulberger CL,Liu Q,Stanley S,Brown J,Sixsmith J,Wolf ID,Fortune SM

    更新日期:2020-11-30 00:00:00

  • AIG1 affects in vitro and in vivo virulence in clinical isolates of Entamoeba histolytica.

    abstract::The disease state of amebiasis, caused by Entamoeba histolytica, varies from asymptomatic to severe manifestations that include dysentery and extraintestinal abscesses. The virulence factors of the pathogen, and host defense mechanisms, contribute to the outcomes of infection; however, the underlying genetic factors, ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006882

    authors: Nakada-Tsukui K,Sekizuka T,Sato-Ebine E,Escueta-de Cadiz A,Ji DD,Tomii K,Kuroda M,Nozaki T

    更新日期:2018-03-19 00:00:00

  • Exosome-mediated miR-146a transfer suppresses type I interferon response and facilitates EV71 infection.

    abstract::Exosomes can transfer genetic materials between cells. Their roles in viral infections are beginning to be appreciated. Researches have shown that exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modulate recipient's cellular response and result in produ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006611

    authors: Fu Y,Zhang L,Zhang F,Tang T,Zhou Q,Feng C,Jin Y,Wu Z

    更新日期:2017-09-14 00:00:00

  • Induction of PGRN by influenza virus inhibits the antiviral immune responses through downregulation of type I interferons signaling.

    abstract::Type I interferons (IFNs) play a critical role in host defense against influenza virus infection, and the mechanism of influenza virus to evade type I IFNs responses remains to be fully understood. Here, we found that progranulin (PGRN) was significantly increased both in vitro and in vivo during influenza virus infec...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008062

    authors: Wei F,Jiang Z,Sun H,Pu J,Sun Y,Wang M,Tong Q,Bi Y,Ma X,Gao GF,Liu J

    更新日期:2019-10-04 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

  • A novel phase variation mechanism in the meningococcus driven by a ligand-responsive repressor and differential spacing of distal promoter elements.

    abstract::Phase variable expression, mediated by high frequency reversible changes in the length of simple sequence repeats, facilitates adaptation of bacterial populations to changing environments and is frequently important in bacterial virulence. Here we elucidate a novel phase variable mechanism for NadA, an adhesin and inv...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000710

    authors: Metruccio MM,Pigozzi E,Roncarati D,Berlanda Scorza F,Norais N,Hill SA,Scarlato V,Delany I

    更新日期:2009-12-01 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

  • The pore-forming toxin listeriolysin O mediates a novel entry pathway of L. monocytogenes into human hepatocytes.

    abstract::Intracellular pathogens have evolved diverse strategies to invade and survive within host cells. Among the most studied facultative intracellular pathogens, Listeria monocytogenes is known to express two invasins-InlA and InlB-that induce bacterial internalization into nonphagocytic cells. The pore-forming toxin liste...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002356

    authors: Vadia S,Arnett E,Haghighat AC,Wilson-Kubalek EM,Tweten RK,Seveau S

    更新日期:2011-11-01 00:00:00

  • The novel interaction between Neisseria gonorrhoeae TdfJ and human S100A7 allows gonococci to subvert host zinc restriction.

    abstract::Neisseria gonorrhoeae causes the sexually-transmitted infection gonorrhea, a global disease that is difficult to treat and for which there is no vaccine. This pathogen employs an arsenal of conserved outer membrane proteins called TonB-dependent transporters (TdTs) that allow the gonococcus to overcome nutritional imm...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007937

    authors: Maurakis S,Keller K,Maxwell CN,Pereira K,Chazin WJ,Criss AK,Cornelissen CN

    更新日期:2019-08-01 00:00:00

  • T follicular helper cells regulate the activation of B lymphocytes and antibody production during Plasmodium vivax infection.

    abstract::Although the importance of humoral immunity to malaria has been established, factors that control antibody production are poorly understood. Follicular helper T cells (Tfh cells) are pivotal for generating high-affinity, long-lived antibody responses. While it has been proposed that expansion of antigen-specific Tfh c...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006484

    authors: Figueiredo MM,Costa PAC,Diniz SQ,Henriques PM,Kano FS,Tada MS,Pereira DB,Soares IS,Martins-Filho OA,Jankovic D,Gazzinelli RT,Antonelli LRDV

    更新日期:2017-07-10 00:00:00