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 generate targeted gene disruptions and mutant phenotypes in any parasitic nematode. Here, we report the development of a method for introducing CRISPR-Cas9-mediated gene disruptions in the human-parasitic threadworm Strongyloides stercoralis. We disrupted the S. stercoralis twitchin gene unc-22, resulting in nematodes with severe motility defects. Ss-unc-22 mutations were resolved by homology-directed repair when a repair template was provided. Omission of a repair template resulted in deletions at the target locus. Ss-unc-22 mutations were heritable; we passed Ss-unc-22 mutants through a host and successfully recovered mutant progeny. Using a similar approach, we also disrupted the unc-22 gene of the rat-parasitic nematode Strongyloides ratti. Our results demonstrate the applicability of CRISPR-Cas9 to parasitic nematodes, and thereby enable future studies of gene function in these medically relevant but previously genetically intractable parasites.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

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

doi

10.1371/journal.ppat.1006675

subject

Has Abstract

pub_date

2017-10-10 00:00:00

pages

e1006675

issue

10

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-17-01106

journal_volume

13

pub_type

杂志文章
  • 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

  • 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

  • Crystal Structure of the Human Cytomegalovirus Glycoprotein B.

    abstract::Human cytomegalovirus (HCMV), a dsDNA, enveloped virus, is a ubiquitous pathogen that establishes lifelong latent infections and caused disease in persons with compromised immune systems, e.g., organ transplant recipients or AIDS patients. HCMV is also a leading cause of congenital viral infections in newborns. Entry ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005227

    authors: Burke HG,Heldwein EE

    更新日期:2015-10-20 00:00:00

  • Listeria monocytogenes cytoplasmic entry induces fetal wastage by disrupting maternal Foxp3+ regulatory T cell-sustained fetal tolerance.

    abstract::Although the intracellular bacterium Listeria monocytogenes has an established predilection for disseminated infection during pregnancy that often results in spontaneous abortion or stillbirth, the specific host-pathogen interaction that dictates these disastrous complications remain incompletely defined. Herein, we d...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002873

    authors: Rowe JH,Ertelt JM,Xin L,Way SS

    更新日期:2012-01-01 00:00:00

  • Effective Respiratory CD8 T-Cell Immunity to Influenza Virus Induced by Intranasal Carbomer-Lecithin-Adjuvanted Non-replicating Vaccines.

    abstract::CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of ge...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006064

    authors: Gasper DJ,Neldner B,Plisch EH,Rustom H,Carrow E,Imai H,Kawaoka Y,Suresh M

    更新日期:2016-12-20 00:00:00

  • Discovery of a Natural Microsporidian Pathogen with a Broad Tissue Tropism in Caenorhabditis elegans.

    abstract::Microbial pathogens often establish infection within particular niches of their host for replication. Determining how infection occurs preferentially in specific host tissues is a key aspect of understanding host-microbe interactions. Here, we describe the discovery of a natural microsporidian parasite of the nematode...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005724

    authors: Luallen RJ,Reinke AW,Tong L,Botts MR,Félix MA,Troemel ER

    更新日期:2016-06-30 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

  • Hepatitis C Virus Stimulates Murine CD8α-Like Dendritic Cells to Produce Type I Interferon in a TRIF-Dependent Manner.

    abstract::Hepatitis C virus (HCV) induces interferon (IFN) stimulated genes in the liver despite of distinct innate immune evasion mechanisms, suggesting that beyond HCV infected cells other cell types contribute to innate immune activation. Upon coculture with HCV replicating cells, human CD141+ myeloid dendritic cells (DC) pr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005736

    authors: Pfaender S,Grabski E,Detje CN,Riebesehl N,Lienenklaus S,Steinmann E,Kalinke U,Pietschmann T

    更新日期:2016-07-06 00:00:00

  • A single mutation in the envelope protein modulates flavivirus antigenicity, stability, and pathogenesis.

    abstract::The structural flexibility or 'breathing' of the envelope (E) protein of flaviviruses allows virions to sample an ensemble of conformations at equilibrium. The molecular basis and functional consequences of virus conformational dynamics are poorly understood. Here, we identified a single mutation at residue 198 (T198F...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006178

    authors: Goo L,VanBlargan LA,Dowd KA,Diamond MS,Pierson TC

    更新日期:2017-02-16 00:00:00

  • The Vibrio cholerae colonization factor GbpA possesses a modular structure that governs binding to different host surfaces.

    abstract::Vibrio cholerae is a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. Colonization of these different niches involves an N-acetylglucosamine binding protein (GbpA) that has been reported to mediate bacterial attachment to both marine chitin and mam...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002373

    authors: Wong E,Vaaje-Kolstad G,Ghosh A,Hurtado-Guerrero R,Konarev PV,Ibrahim AF,Svergun DI,Eijsink VG,Chatterjee NS,van Aalten DM

    更新日期:2012-01-01 00:00:00

  • Na+ Influx Induced by New Antimalarials Causes Rapid Alterations in the Cholesterol Content and Morphology of Plasmodium falciparum.

    abstract::Among the several new antimalarials discovered over the past decade are at least three clinical candidate drugs, each with a distinct chemical structure, that disrupt Na+ homeostasis resulting in a rapid increase in intracellular Na+ concentration ([Na+]i) within the erythrocytic stages of Plasmodium falciparum. At pr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005647

    authors: Das S,Bhatanagar S,Morrisey JM,Daly TM,Burns JM Jr,Coppens I,Vaidya AB

    更新日期:2016-05-26 00:00:00

  • Kaposi's sarcoma associated herpes virus (KSHV) induced COX-2: a key factor in latency, inflammation, angiogenesis, cell survival and invasion.

    abstract::Kaposi's sarcoma (KS), an enigmatic endothelial cell vascular neoplasm, is characterized by the proliferation of spindle shaped endothelial cells, inflammatory cytokines (ICs), growth factors (GFs) and angiogenic factors. KSHV is etiologically linked to KS and expresses its latent genes in KS lesion endothelial cells....

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000777

    authors: Sharma-Walia N,Paul AG,Bottero V,Sadagopan S,Veettil MV,Kerur N,Chandran B

    更新日期:2010-02-12 00:00:00

  • Type I interferon-dependent CCL4 is induced by a cGAS/STING pathway that bypasses viral inhibition and protects infected tissue, independent of viral burden.

    abstract::Type I interferons (T1-IFN) are critical in the innate immune response, acting upon infected and uninfected cells to initiate an antiviral state by expressing genes that inhibit multiple stages of the lifecycle of many viruses. T1-IFN triggers the production of Interferon-Stimulated Genes (ISGs), activating an antivir...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007778

    authors: Parekh NJ,Krouse TE,Reider IE,Hobbs RP,Ward BM,Norbury CC

    更新日期:2019-10-11 00:00:00

  • Cross-Species Transmission and Differential Fate of an Endogenous Retrovirus in Three Mammal Lineages.

    abstract::Endogenous retroviruses (ERVs) arise from retroviruses chromosomally integrated in the host germline. ERVs are common in vertebrate genomes and provide a valuable fossil record of past retroviral infections to investigate the biology and evolution of retroviruses over a deep time scale, including cross-species transmi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005279

    authors: Zhuo X,Feschotte C

    更新日期:2015-11-12 00:00:00

  • Human Immunodeficiency Virus Type 1 Nef Inhibits Autophagy through Transcription Factor EB Sequestration.

    abstract::HIV Nef acts as an anti-autophagic maturation factor through interaction with beclin-1 (BECN1). We report that exposure of macrophages to infectious or non-infectious purified HIV induces toll-like receptor 8 (TLR8) and BECN1 dependent dephosphorylation and nuclear translocation of TFEB and that this correlates with a...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005018

    authors: Campbell GR,Rawat P,Bruckman RS,Spector SA

    更新日期:2015-06-26 00:00:00

  • Quantitative models of the dose-response and time course of inhalational anthrax in humans.

    abstract::Anthrax poses a community health risk due to accidental or intentional aerosol release. Reliable quantitative dose-response analyses are required to estimate the magnitude and timeline of potential consequences and the effect of public health intervention strategies under specific scenarios. Analyses of available data...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003555

    authors: Toth DJ,Gundlapalli AV,Schell WA,Bulmahn K,Walton TE,Woods CW,Coghill C,Gallegos F,Samore MH,Adler FR

    更新日期:2013-08-01 00:00:00

  • Transcriptional activation of the adenoviral genome is mediated by capsid protein VI.

    abstract::Gene expression of DNA viruses requires nuclear import of the viral genome. Human Adenoviruses (Ads), like most DNA viruses, encode factors within early transcription units promoting their own gene expression and counteracting cellular antiviral defense mechanisms. The cellular transcriptional repressor Daxx prevents ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002549

    authors: Schreiner S,Martinez R,Groitl P,Rayne F,Vaillant R,Wimmer P,Bossis G,Sternsdorf T,Marcinowski L,Ruzsics Z,Dobner T,Wodrich H

    更新日期:2012-02-01 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

  • PML/TRIM19-Dependent Inhibition of Retroviral Reverse-Transcription by Daxx.

    abstract::PML (Promyelocytic Leukemia protein), also known as TRIM19, belongs to the family of tripartite motif (TRIM) proteins. PML is mainly expressed in the nucleus, where it forms dynamic structures known as PML nuclear bodies that recruit many other proteins, such as Sp100 and Daxx. While the role of PML/TRIM19 in antivira...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005280

    authors: Dutrieux J,Maarifi G,Portilho DM,Arhel NJ,Chelbi-Alix MK,Nisole S

    更新日期:2015-11-13 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

  • HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes.

    abstract::Lytic herpes simplex virus 1 (HSV-1) infection triggers disruption of transcription termination (DoTT) of most cellular genes, resulting in extensive intergenic transcription. Similarly, cellular stress responses lead to gene-specific transcription downstream of genes (DoG). In this study, we performed a detailed comp...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006954

    authors: Hennig T,Michalski M,Rutkowski AJ,Djakovic L,Whisnant AW,Friedl MS,Jha BA,Baptista MAP,L'Hernault A,Erhard F,Dölken L,Friedel CC

    更新日期:2018-03-26 00:00:00

  • A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine.

    abstract::The effectiveness of the annual influenza vaccine has declined in recent years, especially for the H3N2 component, and is a concern for global public health. A major cause for this lack in effectiveness has been attributed to the egg-based vaccine production process. Substitutions on the hemagglutinin glycoprotein (HA...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006682

    authors: Wu NC,Zost SJ,Thompson AJ,Oyen D,Nycholat CM,McBride R,Paulson JC,Hensley SE,Wilson IA

    更新日期:2017-10-23 00:00:00

  • Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice.

    abstract::The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1009287

    authors: Graham JB,Swarts JL,Leist SR,Schäfer A,Menachery VD,Gralinski LE,Jeng S,Miller DR,Mooney MA,McWeeney SK,Ferris MT,Pardo-Manuel de Villena F,Heise MT,Baric RS,Lund JM

    更新日期:2021-01-29 00:00:00

  • Global synonymous mutagenesis identifies cis-acting RNA elements that regulate HIV-1 splicing and replication.

    abstract::The ~9.5 kilobase HIV-1 genome contains RNA sequences and structures that control many aspects of viral replication, including transcription, splicing, nuclear export, translation, packaging and reverse transcription. Nonetheless, chemical probing and other approaches suggest that the HIV-1 genome may contain many mor...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006824

    authors: Takata MA,Soll SJ,Emery A,Blanco-Melo D,Swanstrom R,Bieniasz PD

    更新日期:2018-01-29 00:00:00

  • Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    abstract::Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been w...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004689

    authors: Creek DJ,Mazet M,Achcar F,Anderson J,Kim DH,Kamour R,Morand P,Millerioux Y,Biran M,Kerkhoven EJ,Chokkathukalam A,Weidt SK,Burgess KE,Breitling R,Watson DG,Bringaud F,Barrett MP

    更新日期:2015-03-16 00:00:00

  • A Homolog Pentameric Complex Dictates Viral Epithelial Tropism, Pathogenicity and Congenital Infection Rate in Guinea Pig Cytomegalovirus.

    abstract::In human cytomegalovirus (HCMV), tropism to epithelial and endothelial cells is dependent upon a pentameric complex (PC). Given the structure of the placenta, the PC is potentially an important neutralizing antibody target antigen against congenital infection. The guinea pig is the only small animal model for congenit...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005755

    authors: Coleman S,Choi KY,Root M,McGregor A

    更新日期:2016-07-07 00:00:00

  • NsrR, GadE, and GadX interplay in repressing expression of the Escherichia coli O157:H7 LEE pathogenicity island in response to nitric oxide.

    abstract::Expression of genes of the locus of enterocyte effacement (LEE) is essential for adherence of enterohemorrhagic Escherichia coli (EHEC) to intestinal epithelial cells. Gut factors that may modulate LEE gene expression may therefore influence the outcome of the infection. Because nitric oxide (NO) is a critical effecto...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003874

    authors: Branchu P,Matrat S,Vareille M,Garrivier A,Durand A,Crépin S,Harel J,Jubelin G,Gobert AP

    更新日期:2014-01-01 00:00:00

  • Emodepside has sex-dependent immobilizing effects on adult Brugia malayi due to a differentially spliced binding pocket in the RCK1 region of the SLO-1 K channel.

    abstract::Filariae are parasitic nematodes that are transmitted to their definitive host as third-stage larvae by arthropod vectors like mosquitoes. Filariae cause diseases including: lymphatic filariasis with distressing and disturbing symptoms like elephantiasis; and river blindness. Filarial diseases affect millions of peopl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008041

    authors: Kashyap SS,Verma S,Voronin D,Lustigman S,Kulke D,Robertson AP,Martin RJ

    更新日期:2019-09-25 00:00:00

  • Transcytosis subversion by M cell-to-enterocyte spread promotes Shigella flexneri and Listeria monocytogenes  intracellular bacterial dissemination.

    abstract::Microfold (M) cell host-pathogen interaction studies would benefit from the visual analysis of dynamic cellular and microbial interplays. We adapted a human in vitro M cell model to physiological bacterial infections, expression of fluorescent localization reporters and long-term three-dimensional time-lapse microscop...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008446

    authors: Rey C,Chang YY,Latour-Lambert P,Varet H,Proux C,Legendre R,Coppée JY,Enninga J

    更新日期:2020-04-13 00:00:00

  • Multiple translocation of the AVR-Pita effector gene among chromosomes of the rice blast fungus Magnaporthe oryzae and related species.

    abstract::Magnaporthe oryzae is the causal agent of rice blast disease, a devastating problem worldwide. This fungus has caused breakdown of resistance conferred by newly developed commercial cultivars. To address how the rice blast fungus adapts itself to new resistance genes so quickly, we examined chromosomal locations of AV...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002147

    authors: Chuma I,Isobe C,Hotta Y,Ibaragi K,Futamata N,Kusaba M,Yoshida K,Terauchi R,Fujita Y,Nakayashiki H,Valent B,Tosa Y

    更新日期:2011-07-01 00:00:00