Comprehensive analysis of iron utilization by Mycobacterium tuberculosis.


:Iron is essential for nearly all bacterial pathogens, including Mycobacterium tuberculosis (Mtb), but is severely limited in the human host. To meet its iron needs, Mtb secretes siderophores, small molecules with high affinity for iron, and takes up iron-loaded mycobactins (MBT) and carboxymycobactins (cMBT), from the environment. Mtb is also capable of utilizing heme and hemoglobin which contain more than 70% of the iron in the human body. However, many components of these iron acquisition pathways are still unknown. In this study, a high-density transposon mutagenesis coupled with deep sequencing (TnSeq) showed that Mtb exhibits nearly opposite requirements for 165 genes in the presence of heme and hemoglobin versus MBT and cMBT as iron sources. The ESX-3 secretion system was assessed as essential for siderophore-mediated iron uptake and, surprisingly, also for heme utilization by Mtb. Predictions derived from the TnSeq analysis were validated by growth experiments with isogenic Mtb mutants. These results showed that (i) the efflux pump MmpL5 plays a dominant role in siderophore secretion, (ii) the Rv2047c protein is essential for growth of Mtb in the presence of mycobactin, and (iii) the transcriptional repressor Zur is required for heme utilization by Mtb. The novel genetic determinants of iron utilization revealed in this study will stimulate further experiments in this important area of Mtb physiology.


PLoS Pathog


PLoS pathogens


Zhang L,Hendrickson RC,Meikle V,Lefkowitz EJ,Ioerger TR,Niederweis M




Has Abstract


2020-02-18 00:00:00














  • Innate killing of Leishmania donovani by macrophages of the splenic marginal zone requires IRF-7.

    abstract::Highly phagocytic macrophages line the marginal zone (MZ) of the spleen and the lymph node subcapsular sinus. Although these macrophages have been attributed with a variety of functions, including the uptake and clearance of blood and lymph-borne pathogens, little is known about the effector mechanisms they employ aft...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Phillips R,Svensson M,Aziz N,Maroof A,Brown N,Beattie L,Signoret N,Kaye PM

    更新日期:2010-03-12 00:00:00

  • Epstein-Barr virus LMP1 manipulates the content and functions of extracellular vesicles to enhance metastatic potential of recipient cells.

    abstract::Extracellular vesicles (EV) mediate intercellular communication events and alterations in normal vesicle content contribute to function and disease initiation or progression. The ability to package a variety of cargo and transmit molecular information between cells renders EVs important mediators of cell-to-cell cross...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Nkosi D,Sun L,Duke LC,Meckes DG Jr

    更新日期:2020-12-31 00:00:00

  • Inhibition of JNK signaling in the Asian malaria vector Anopheles stephensi extends mosquito longevity and improves resistance to Plasmodium falciparum infection.

    abstract::Malaria is a global health concern caused by infection with Plasmodium parasites. With rising insecticide and drug resistance, there is a critical need to develop novel control strategies, including strategies to block parasite sporogony in key mosquito vector species. MAPK signaling pathways regulated by extracellula...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Souvannaseng L,Hun LV,Baker H,Klyver JM,Wang B,Pakpour N,Bridgewater JM,Napoli E,Giulivi C,Riehle MA,Luckhart S

    更新日期:2018-11-29 00:00:00

  • Prolonged influenza virus shedding and emergence of antiviral resistance in immunocompromised patients and ferrets.

    abstract::Immunocompromised individuals tend to suffer from influenza longer with more serious complications than otherwise healthy patients. Little is known about the impact of prolonged infection and the efficacy of antiviral therapy in these patients. Among all 189 influenza A virus infected immunocompromised patients admitt...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: van der Vries E,Stittelaar KJ,van Amerongen G,Veldhuis Kroeze EJ,de Waal L,Fraaij PL,Meesters RJ,Luider TM,van der Nagel B,Koch B,Vulto AG,Schutten M,Osterhaus AD

    更新日期:2013-01-01 00:00:00

  • Development of a transformation system for Chlamydia trachomatis: restoration of glycogen biosynthesis by acquisition of a plasmid shuttle vector.

    abstract::Chlamydia trachomatis remains one of the few major human pathogens for which there is no transformation system. C. trachomatis has a unique obligate intracellular developmental cycle. The extracellular infectious elementary body (EB) is an infectious, electron-dense structure that, following host cell infection, diffe...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Wang Y,Kahane S,Cutcliffe LT,Skilton RJ,Lambden PR,Clarke IN

    更新日期:2011-09-01 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


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

    更新日期:2016-07-07 00:00:00

  • Pathogenicity of Mycobacterium tuberculosis is expressed by regulating metabolic thresholds of the host macrophage.

    abstract::The success of Mycobacterium tuberculosis as a pathogen derives from its facile adaptation to the intracellular milieu of human macrophages. To explore this process, we asked whether adaptation also required interference with the metabolic machinery of the host cell. Temporal profiling of the metabolic flux, in cells ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Mehrotra P,Jamwal SV,Saquib N,Sinha N,Siddiqui Z,Manivel V,Chatterjee S,Rao KV

    更新日期:2014-07-24 00:00:00

  • Preservation of tetherin and CD4 counter-activities in circulating Vpu alleles despite extensive sequence variation within HIV-1 infected individuals.

    abstract::The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires thro...

    journal_title:PLoS pathogens

    pub_type: 临床试验,杂志文章


    authors: Pickering S,Hué S,Kim EY,Reddy S,Wolinsky SM,Neil SJ

    更新日期:2014-01-01 00:00:00

  • Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer.

    abstract::Vaccinia virus A33 is an extracellular enveloped virus (EEV)-specific type II membrane glycoprotein that is essential for efficient EEV formation and long-range viral spread within the host. A33 is a target for neutralizing antibody responses against EEV. In this study, we produced seven murine anti-A33 monoclonal ant...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Matho MH,Schlossman A,Meng X,Benhnia MR,Kaever T,Buller M,Doronin K,Parker S,Peters B,Crotty S,Xiang Y,Zajonc DM

    更新日期:2015-09-01 00:00:00

  • Mobile genetic element SCCmec-encoded psm-mec RNA suppresses translation of agrA and attenuates MRSA virulence.

    abstract::Community acquired-methicillin resistant Staphylococcus aureus (CA-MRSA) is a socially problematic pathogen that infects healthy individuals, causing severe disease. CA-MRSA is more virulent than hospital associated-MRSA (HA-MRSA). The underlying mechanism for the high virulence of CA-MRSA is not known. The transcript...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Kaito C,Saito Y,Ikuo M,Omae Y,Mao H,Nagano G,Fujiyuki T,Numata S,Han X,Obata K,Hasegawa S,Yamaguchi H,Inokuchi K,Ito T,Hiramatsu K,Sekimizu K

    更新日期:2013-01-01 00:00:00

  • The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein.

    abstract::PB1-F2 is a 90 amino acid protein that is expressed from the +1 open reading frame in the PB1 gene of some influenza A viruses and has been shown to contribute to viral pathogenicity. Notably, a serine at position 66 (66S) in PB1-F2 is known to increase virulence compared to an isogenic virus with an asparagine (66N) ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Varga ZT,Ramos I,Hai R,Schmolke M,García-Sastre A,Fernandez-Sesma A,Palese P

    更新日期:2011-06-01 00:00:00

  • Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria.

    abstract::Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships bet...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Barber BE,William T,Grigg MJ,Parameswaran U,Piera KA,Price RN,Yeo TW,Anstey NM

    更新日期:2015-01-08 00:00:00

  • Lipid exchange between Borrelia burgdorferi and host cells.

    abstract::Borrelia burgdorferi, the agent of Lyme disease, has cholesterol and cholesterol-glycolipids that are essential for bacterial fitness, are antigenic, and could be important in mediating interactions with cells of the eukaryotic host. We show that the spirochetes can acquire cholesterol from plasma membranes of epithel...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Crowley JT,Toledo AM,LaRocca TJ,Coleman JL,London E,Benach JL

    更新日期:2013-01-01 00:00:00

  • Analysis of the SUMO2 Proteome during HSV-1 Infection.

    abstract::Covalent linkage to members of the small ubiquitin-like (SUMO) family of proteins is an important mechanism by which the functions of many cellular proteins are regulated. Sumoylation has roles in the control of protein stability, activity and localization, and is involved in the regulation of transcription, gene expr...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Sloan E,Tatham MH,Groslambert M,Glass M,Orr A,Hay RT,Everett RD

    更新日期:2015-07-22 00:00:00

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

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    journal_title:PLoS pathogens

    pub_type: 杂志文章


    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

  • Correction: HTLV-1 bZIP Factor Enhances T-cell Proliferation by Impeding the Suppressive Signaling of Co-inhibitory Receptors.

    abstract::[This corrects the article DOI: 10.1371/journal.ppat.1006120.]. ...

    journal_title:PLoS pathogens

    pub_type: 已发布勘误


    authors: Kinosada H,Yasunaga JI,Shimura K,Miyazato P,Onishi C,Iyoda T,Inaba K,Matsuoka M

    更新日期:2017-02-23 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


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

    更新日期:2016-06-30 00:00:00

  • Modelling the evolutionary dynamics of viruses within their hosts: a case study using high-throughput sequencing.

    abstract::Uncovering how natural selection and genetic drift shape the evolutionary dynamics of virus populations within their hosts can pave the way to a better understanding of virus emergence. Mathematical models already play a leading role in these studies and are intended to predict future emergences. Here, using high-thro...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Fabre F,Montarry J,Coville J,Senoussi R,Simon V,Moury B

    更新日期:2012-01-01 00:00:00

  • IL-27 signalling regulates glycolysis in Th1 cells to limit immunopathology during infection.

    abstract::Inflammation is critical for controlling pathogens, but also responsible for symptoms of infectious diseases. IL-27 is an important regulator of inflammation and can limit development of IFNγ-producing Tbet+ CD4+ T (Th1) cells. IL-27 is thought to do this by stimulating IL-10 production by CD4+ T cells, but the underl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Montes de Oca M,de Labastida Rivera F,Winterford C,Frame TCM,Ng SS,Amante FH,Edwards CL,Bukali L,Wang Y,Uzonna JE,Kuns RD,Zhang P,Kabat A,Klein Geltink RI,Pearce EJ,Hill GR,Engwerda CR

    更新日期:2020-10-13 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


    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

  • HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

    abstract::Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Erdmann N,Du VY,Carlson J,Schaefer M,Jureka A,Sterrett S,Yue L,Dilernia D,Lakhi S,Tang J,Sidney J,Gilmour J,Allen S,Hunter E,Heath S,Bansal A,Goepfert PA

    更新日期:2015-08-24 00:00:00

  • Broadly protective monoclonal antibodies against H3 influenza viruses following sequential immunization with different hemagglutinins.

    abstract::As targets of adaptive immunity, influenza viruses are characterized by the fluidity with which they respond to the selective pressure applied by neutralizing antibodies. This mutability of structural determinants of protective immunity is the obstacle in developing universal influenza vaccines. Towards the developmen...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Wang TT,Tan GS,Hai R,Pica N,Petersen E,Moran TM,Palese P

    更新日期:2010-02-26 00:00:00

  • Trypanin, a component of the flagellar Dynein regulatory complex, is essential in bloodstream form African trypanosomes.

    abstract::The Trypanosoma brucei flagellum is a multifunctional organelle with critical roles in motility, cellular morphogenesis, and cell division. Although motility is thought to be important throughout the trypanosome lifecycle, most studies of flagellum structure and function have been restricted to the procyclic lifecycle...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Ralston KS,Hill KL

    更新日期:2006-09-01 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


    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

  • Molecular phylodynamics of the heterosexual HIV epidemic in the United Kingdom.

    abstract::The heterosexual risk group has become the largest HIV infected group in the United Kingdom during the last 10 years, but little is known of the network structure and dynamics of viral transmission in this group. The overwhelming majority of UK heterosexual infections are of non-B HIV subtypes, indicating viruses orig...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Hughes GJ,Fearnhill E,Dunn D,Lycett SJ,Rambaut A,Leigh Brown AJ,UK HIV Drug Resistance Collaboration.

    更新日期:2009-09-01 00:00:00

  • Key interplay between the co-opted sorting nexin-BAR proteins and PI3P phosphoinositide in the formation of the tombusvirus replicase.

    abstract::Positive-strand RNA viruses replicate in host cells by forming large viral replication organelles, which harbor numerous membrane-bound viral replicase complexes (VRCs). In spite of its essential role in viral replication, the biogenesis of the VRCs is not fully understood. The authors identified critical roles of cel...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Feng Z,Kovalev N,Nagy PD

    更新日期:2020-12-28 00:00:00

  • High content phenotypic cell-based visual screen identifies Mycobacterium tuberculosis acyltrehalose-containing glycolipids involved in phagosome remodeling.

    abstract::The ability of the tubercle bacillus to arrest phagosome maturation is considered one major mechanism that allows its survival within host macrophages. To identify mycobacterial genes involved in this process, we developed a high throughput phenotypic cell-based assay enabling individual sub-cellular analysis of over ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Brodin P,Poquet Y,Levillain F,Peguillet I,Larrouy-Maumus G,Gilleron M,Ewann F,Christophe T,Fenistein D,Jang J,Jang MS,Park SJ,Rauzier J,Carralot JP,Shrimpton R,Genovesio A,Gonzalo-Asensio JA,Puzo G,Martin C,Brosch R

    更新日期:2010-09-09 00:00:00

  • A leucine aminopeptidase is involved in kinetoplast DNA segregation in Trypanosoma brucei.

    abstract::The kinetoplast (k), the uniquely packaged mitochondrial DNA of trypanosomatid protists is formed by a catenated network of minicircles and maxicircles that divide and segregate once each cell cycle. Although many proteins involved in kDNA replication and segregation are now known, several key steps in the replication...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Peña-Diaz P,Vancová M,Resl C,Field MC,Lukeš J

    更新日期:2017-04-07 00:00:00

  • The Arabidopsis resistance-like gene SNC1 is activated by mutations in SRFR1 and contributes to resistance to the bacterial effector AvrRps4.

    abstract::The SUPPRESSOR OF rps4-RLD1 (SRFR1) gene was identified based on enhanced AvrRps4-triggered resistance in the naturally susceptible Arabidopsis accession RLD. No other phenotypic effects were recorded, and the extent of SRFR1 involvement in regulating effector-triggered immunity was unknown. Here we show that mutation...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Kim SH,Gao F,Bhattacharjee S,Adiasor JA,Nam JC,Gassmann W

    更新日期:2010-11-04 00:00:00

  • DENV up-regulates the HMG-CoA reductase activity through the impairment of AMPK phosphorylation: A potential antiviral target.

    abstract::Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a choles...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Soto-Acosta R,Bautista-Carbajal P,Cervantes-Salazar M,Angel-Ambrocio AH,Del Angel RM

    更新日期:2017-04-06 00:00:00