Evidence that intracellular stages of Leishmania major utilize amino sugars as a major carbon source.

Abstract:

:Intracellular parasites, such as Leishmania spp, must acquire suitable carbon sources from the host cell in order to replicate. Here we present evidence that intracellular amastigote stages of Leishmania exploit amino sugars in the phagolysosome of mammalian macrophages as a source of carbon and energy. L. major parasites are capable of using N-acetylglucosamine and glucosamine as primarily carbon sources and contain key enzymes required for conversion of these sugars to fructose-6-phosphate. The last step in this pathway is catalyzed by glucosamine-6-phosphate deaminase (GND), which was targeted to glycosomes via a canonical C-terminal targeting signal when expressed as a GFP fusion protein. Mutant parasites lacking GND were unable to grow in medium containing amino sugars as sole carbohydrate source and rapidly lost viability, concomitant with the hyper-accumulation of hexosamine-phosphates. Expression of native GND, but not a cytosolic form of GND, in Δgnd parasites restored hexosamine-dependent growth, indicating that toxicity is due to depletion of glycosomal pools of ATP. Non-lethal increases in hexosamine phosphate levels in both Δgnd and wild type parasites was associated with a defect in promastigote metacyclogenesis, suggesting that hexosamine phosphate levels may influence parasite differentiation. Promastigote and amastigote stages of the Δgnd mutant were unable to replicate within macrophages and were either completely cleared or exhibited reduced lesion development in highly susceptible Balb/c mice. Our results suggest that hexosamines are a major class of sugars in the macrophage phagolysosome and that catabolism of scavenged amino sugars is required to sustain essential metabolic pathways and prevent hexosamine toxicity.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Naderer T,Heng J,McConville MJ

doi

10.1371/journal.ppat.1001245

subject

Has Abstract

pub_date

2010-12-23 00:00:00

pages

e1001245

issue

12

eissn

1553-7366

issn

1553-7374

journal_volume

6

pub_type

杂志文章
  • Induction of type I interferon signaling determines the relative pathogenicity of Staphylococcus aureus strains.

    abstract::The tremendous success of S. aureus as a human pathogen has been explained primarily by its array of virulence factors that enable the organism to evade host immunity. Perhaps equally important, but less well understood, is the importance of the intensity of the host response in determining the extent of pathology ind...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003951

    authors: Parker D,Planet PJ,Soong G,Narechania A,Prince A

    更新日期:2014-02-20 00:00:00

  • Picornavirus infection induces temporal release of multiple extracellular vesicle subsets that differ in molecular composition and infectious potential.

    abstract::Several naked virus species, including members of the Picornaviridae family, have recently been described to escape their host cells and spread infection via enclosure in extracellular vesicles (EV). EV are 50-300 nm sized lipid membrane-enclosed particles produced by all cells that are broadly recognized for playing ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007594

    authors: van der Grein SG,Defourny KAY,Rabouw HH,Galiveti CR,Langereis MA,Wauben MHM,Arkesteijn GJA,van Kuppeveld FJM,Nolte-'t Hoen ENM

    更新日期:2019-02-19 00:00:00

  • Polyfunctional type-1, -2, and -17 CD8⁺ T cell responses to apoptotic self-antigens correlate with the chronic evolution of hepatitis C virus infection.

    abstract::Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8⁺ T cell responses in various infectious diseases. We found that the emergence of a large population of autoreactive CD8⁺ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002759

    authors: Franceschini D,Del Porto P,Piconese S,Trella E,Accapezzato D,Paroli M,Morrone S,Piccolella E,Spada E,Mele A,Sidney J,Sette A,Barnaba V

    更新日期:2012-01-01 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

  • Natural transformation facilitates transfer of transposons, integrons and gene cassettes between bacterial species.

    abstract::We have investigated to what extent natural transformation acting on free DNA substrates can facilitate transfer of mobile elements including transposons, integrons and/or gene cassettes between bacterial species. Naturally transformable cells of Acinetobacter baylyi were exposed to DNA from integron-carrying strains ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002837

    authors: Domingues S,Harms K,Fricke WF,Johnsen PJ,da Silva GJ,Nielsen KM

    更新日期:2012-01-01 00:00:00

  • EhC2B, a C2 domain-containing protein, promotes erythrophagocytosis in Entamoeba histolytica via actin nucleation.

    abstract::Remodelling of the actin cytoskeleton in response to external stimuli is obligatory for many cellular processes in the amoebic cell. A rapid and local rearrangement of the actin cytoskeleton is required for the development of the cellular protrusions during phagocytosis, trogocytosis, migration, and invasion. Here, we...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008489

    authors: Tripathi A,Jain M,Chandra M,Parveen S,Yadav R,Collins BM,Maiti S,Datta S

    更新日期:2020-05-04 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

  • Nanoformulations of Rilpivirine for Topical Pericoital and Systemic Coitus-Independent Administration Efficiently Prevent HIV Transmission.

    abstract::Vaginal HIV transmission accounts for the majority of new infections worldwide. Currently, multiple efforts to prevent HIV transmission are based on pre-exposure prophylaxis with various antiretroviral drugs. Here, we describe two novel nanoformulations of the reverse transcriptase inhibitor rilpivirine for pericoital...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005075

    authors: Kovarova M,Council OD,Date AA,Long JM,Nochi T,Belshan M,Shibata A,Vincent H,Baker CE,Thayer WO,Kraus G,Lachaud-Durand S,Williams P,Destache CJ,Garcia JV

    更新日期:2015-08-13 00:00:00

  • Accurate prediction of secreted substrates and identification of a conserved putative secretion signal for type III secretion systems.

    abstract::The type III secretion system is an essential component for virulence in many Gram-negative bacteria. Though components of the secretion system apparatus are conserved, its substrates--effector proteins--are not. We have used a novel computational approach to confidently identify new secreted effectors by integrating ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000375

    authors: Samudrala R,Heffron F,McDermott JE

    更新日期:2009-04-01 00:00:00

  • In vivo administration of a JAK3 inhibitor during acute SIV infection leads to significant increases in viral load during chronic infection.

    abstract::The studies reported herein are the first to document the effect of the in vivo administration of a JAK3 inhibitor for defining the potential role of NK cells during acute SIV infection of a group of 15 rhesus macaques (RM). An additional group of 16 MHC/KIR typed RM was included as controls. The previously optimized ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003929

    authors: Takahashi Y,Byrareddy SN,Albrecht C,Brameier M,Walter L,Mayne AE,Dunbar P,Russo R,Little DM,Villinger T,Khowawisetsut L,Pattanapanyasat K,Villinger F,Ansari AA

    更新日期:2014-03-06 00:00:00

  • The TIR Homologue Lies near Resistance Genes in Staphylococcus aureus, Coupling Modulation of Virulence and Antimicrobial Susceptibility.

    abstract::Toll/interleukin-1 receptor (TIR) domains in Toll-like receptors are essential for initiating and propagating the eukaryotic innate immune signaling cascade. Here, we investigate TirS, a Staphylococcus aureus TIR mimic that is part of a novel bacterial invasion mechanism. Its ectopic expression in eukaryotic cells inh...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006092

    authors: Patot S,Imbert PR,Baude J,Martins Simões P,Campergue JB,Louche A,Nijland R,Bès M,Tristan A,Laurent F,Fischer A,Schrenzel J,Vandenesch F,Salcedo SP,François P,Lina G

    更新日期:2017-01-06 00:00:00

  • Dual miRNA targeting restricts host range and attenuates neurovirulence of flaviviruses.

    abstract::Mosquito-borne flaviviruses are among the most significant arboviral pathogens worldwide. Vaccinations and mosquito population control programs remain the most reliable means for flavivirus disease prevention, and live attenuated viruses remain one of the most attractive flavivirus vaccine platforms. Some live attenua...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004852

    authors: Tsetsarkin KA,Liu G,Kenney H,Bustos-Arriaga J,Hanson CT,Whitehead SS,Pletnev AG

    更新日期:2015-04-23 00:00:00

  • Phospho-dependent Regulation of SAMHD1 Oligomerisation Couples Catalysis and Restriction.

    abstract::SAMHD1 restricts HIV-1 infection of myeloid-lineage and resting CD4+ T-cells. Most likely this occurs through deoxynucleoside triphosphate triphosphohydrolase activity that reduces cellular dNTP to a level where reverse transcriptase cannot function, although alternative mechanisms have been proposed recently. Here, w...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1005194

    authors: Arnold LH,Groom HC,Kunzelmann S,Schwefel D,Caswell SJ,Ordonez P,Mann MC,Rueschenbaum S,Goldstone DC,Pennell S,Howell SA,Stoye JP,Webb M,Taylor IA,Bishop KN

    更新日期:2015-10-02 00:00:00

  • Diverse pathways of escape from all well-characterized VRC01-class broadly neutralizing HIV-1 antibodies.

    abstract::Many broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus type 1 (HIV-1) were shown effective in animal models, and are currently evaluated in clinical trials. However, use of these antibodies in humans is hampered by the rapid emergence of resistant viruses. Here we show that soft-randomizatio...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1007238

    authors: Otsuka Y,Schmitt K,Quinlan BD,Gardner MR,Alfant B,Reich A,Farzan M,Choe H

    更新日期:2018-08-20 00:00:00

  • Slit2/Robo4 signaling modulates HIV-1 gp120-induced lymphatic hyperpermeability.

    abstract::Dissemination of HIV in the host involves transit of the virus and virus-infected cells across the lymphatic endothelium. HIV may alter lymphatic endothelial permeability to foster dissemination, but the mechanism is largely unexplored. Using a primary human lymphatic endothelial cell model, we found that HIV-1 envelo...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002461

    authors: Zhang X,Yu J,Kuzontkoski PM,Zhu W,Li DY,Groopman JE

    更新日期:2012-01-01 00:00:00

  • Kaposi's sarcoma herpesvirus microRNAs induce metabolic transformation of infected cells.

    abstract::Altered cell metabolism is inherently connected with pathological conditions including cancer and viral infections. Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS). KS tumour cells display features of lymphatic endothelial differentiation and in their vast majority are ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004400

    authors: Yogev O,Lagos D,Enver T,Boshoff C

    更新日期:2014-09-25 00:00:00

  • Correction: Zika Virus infection of rhesus macaques leads to viral persistence in multiple tissues.

    abstract::[This corrects the article DOI: 10.1371/journal.ppat.1006219.]. ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章,已发布勘误

    doi:10.1371/journal.ppat.1006317

    authors: Hirsch AJ,Smith JL,Haese NN,Broeckel RM,Parkins CJ,Kreklywich C,DeFilippis VR,Denton M,Smith PP,Messer WB,Colgin LM,Ducore RM,Grigsby PL,Hennebold JD,Swanson T,Legasse AW,Axthelm MK,MacAllister R,Wiley CA,Nelson JA

    更新日期:2017-04-05 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

  • Definition of herpes simplex virus type 1 helper activities for adeno-associated virus early replication events.

    abstract::The human parvovirus Adeno-Associated Virus (AAV) type 2 can only replicate in cells co-infected with a helper virus, such as Adenovirus or Herpes Simplex Virus type 1 (HSV-1); whereas, in the absence of a helper virus, it establishes a latent infection. Previous studies demonstrated that the ternary HSV-1 helicase/pr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000340

    authors: Alazard-Dany N,Nicolas A,Ploquin A,Strasser R,Greco A,Epstein AL,Fraefel C,Salvetti A

    更新日期:2009-03-01 00:00:00

  • HIV capsid is a tractable target for small molecule therapeutic intervention.

    abstract::Despite a high current standard of care in antiretroviral therapy for HIV, multidrug-resistant strains continue to emerge, underscoring the need for additional novel mechanism inhibitors that will offer expanded therapeutic options in the clinic. We report a new class of small molecule antiretroviral compounds that di...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001220

    authors: Blair WS,Pickford C,Irving SL,Brown DG,Anderson M,Bazin R,Cao J,Ciaramella G,Isaacson J,Jackson L,Hunt R,Kjerrstrom A,Nieman JA,Patick AK,Perros M,Scott AD,Whitby K,Wu H,Butler SL

    更新日期:2010-12-09 00:00:00

  • Programmed protection of foreign DNA from restriction allows pathogenicity island exchange during pneumococcal transformation.

    abstract::In bacteria, transformation and restriction-modification (R-M) systems play potentially antagonistic roles. While the former, proposed as a form of sexuality, relies on internalized foreign DNA to create genetic diversity, the latter degrade foreign DNA to protect from bacteriophage attack. The human pathogen Streptoc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1003178

    authors: Johnston C,Martin B,Granadel C,Polard P,Claverys JP

    更新日期:2013-02-01 00:00:00

  • Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.

    abstract::The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs,...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1001266

    authors: Reichelt M,Wang L,Sommer M,Perrino J,Nour AM,Sen N,Baiker A,Zerboni L,Arvin AM

    更新日期:2011-02-03 00:00:00

  • The binding of triclosan to SmeT, the repressor of the multidrug efflux pump SmeDEF, induces antibiotic resistance in Stenotrophomonas maltophilia.

    abstract::The wide utilization of biocides poses a concern on the impact of these compounds on natural bacterial populations. Furthermore, it has been demonstrated that biocides can select, at least in laboratory experiments, antibiotic resistant bacteria. This situation has raised concerns, not just on scientists and clinician...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1002103

    authors: Hernández A,Ruiz FM,Romero A,Martínez JL

    更新日期:2011-06-01 00:00:00

  • Ecotin, a microbial inhibitor of serine proteases, blocks multiple complement dependent and independent microbicidal activities of human serum.

    abstract::Ecotin is a serine protease inhibitor produced by hundreds of microbial species, including pathogens. Here we show, that ecotin orthologs from Escherichia coli, Yersinia pestis, Pseudomonas aeruginosa and Leishmania major are potent inhibitors of MASP-1 and MASP-2, the two key activator proteases of the complement lec...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1008232

    authors: Nagy ZA,Szakács D,Boros E,Héja D,Vígh E,Sándor N,Józsi M,Oroszlán G,Dobó J,Gál P,Pál G

    更新日期:2019-12-20 00:00:00

  • Diverse heterologous primary infections radically alter immunodominance hierarchies and clinical outcomes following H7N9 influenza challenge in mice.

    abstract::The recent emergence of a novel H7N9 influenza A virus (IAV) causing severe human infections in China raises concerns about a possible pandemic. The lack of pre-existing neutralizing antibodies in the broader population highlights the potential protective role of IAV-specific CD8(+) cytotoxic T lymphocyte (CTL) memory...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004642

    authors: Duan S,Meliopoulos VA,McClaren JL,Guo XZ,Sanders CJ,Smallwood HS,Webby RJ,Schultz-Cherry SL,Doherty PC,Thomas PG

    更新日期:2015-02-10 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

  • Serum-dependent selective expression of EhTMKB1-9, a member of Entamoeba histolytica B1 family of transmembrane kinases.

    abstract::Entamoeba histolytica transmembrane kinases (EhTMKs) can be grouped into six distinct families on the basis of motifs and sequences. Analysis of the E. histolytica genome revealed the presence of 35 EhTMKB1 members on the basis of sequence identity (>or=95%). Only six homologs were full length containing an extracellu...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1000929

    authors: Shrimal S,Bhattacharya S,Bhattacharya A

    更新日期:2010-06-03 00:00:00

  • Creating an arsenal of Adeno-associated virus (AAV) gene delivery stealth vehicles.

    abstract::The Adeno-associated virus (AAV) gene delivery system is ushering in a new and exciting era in the United States; following the first approved gene therapy (Glybera) in Europe, the FDA has approved a second therapy, Luxturna [1]. However, challenges to this system remain. In viral gene therapy, the surface of the caps...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1006929

    authors: Smith JK,Agbandje-McKenna M

    更新日期:2018-05-03 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

  • Toxin-induced necroptosis is a major mechanism of Staphylococcus aureus lung damage.

    abstract::Staphylococcus aureus USA300 strains cause a highly inflammatory necrotizing pneumonia. The virulence of this strain has been attributed to its expression of multiple toxins that have diverse targets including ADAM10, NLRP3 and CD11b. We demonstrate that induction of necroptosis through RIP1/RIP3/MLKL signaling is a m...

    journal_title:PLoS pathogens

    pub_type: 杂志文章

    doi:10.1371/journal.ppat.1004820

    authors: Kitur K,Parker D,Nieto P,Ahn DS,Cohen TS,Chung S,Wachtel S,Bueno S,Prince A

    更新日期:2015-04-16 00:00:00