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














  • Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs.

    abstract::Parvoviruses exploit transferrin receptor type-1 (TfR) for cellular entry in carnivores, and specific interactions are key to control of host range. We show that several key mutations acquired by TfR during the evolution of Caniforms (dogs and related species) modified the interactions with parvovirus capsids by reduc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Kaelber JT,Demogines A,Harbison CE,Allison AB,Goodman LB,Ortega AN,Sawyer SL,Parrish CR

    更新日期:2012-01-01 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


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

    更新日期:2018-01-29 00:00:00

  • Influenza HA subtypes demonstrate divergent phenotypes for cleavage activation and pH of fusion: implications for host range and adaptation.

    abstract::The influenza A virus (IAV) HA protein must be activated by host cells proteases in order to prime the molecule for fusion. Consequently, the availability of activating proteases and the susceptibility of HA to protease activity represents key factors in facilitating virus infection. As such, understanding the intrica...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Galloway SE,Reed ML,Russell CJ,Steinhauer DA

    更新日期:2013-02-01 00:00:00

  • A novel mode of control of nickel uptake by a multifunctional metallochaperone.

    abstract::Cellular metal homeostasis is a critical process for all organisms, requiring tight regulation. In the major pathogen Helicobacter pylori, the acquisition of nickel is an essential virulence determinant as this metal is a cofactor for the acid-resistance enzyme, urease. Nickel uptake relies on the NixA permease and th...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Denic M,Turlin E,Michel V,Fischer F,Khorasani-Motlagh M,Zamble D,Vinella D,de Reuse H

    更新日期:2021-01-14 00:00:00

  • Rift Valley fever virus NSs protein promotes post-transcriptional downregulation of protein kinase PKR and inhibits eIF2alpha phosphorylation.

    abstract::Rift Valley fever virus (RVFV) (genus Phlebovirus, family Bunyaviridae) is a negative-stranded RNA virus with a tripartite genome. RVFV is transmitted by mosquitoes and causes fever and severe hemorrhagic illness among humans, and fever and high rates of abortions in livestock. A nonstructural RVFV NSs protein inhibit...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Ikegami T,Narayanan K,Won S,Kamitani W,Peters CJ,Makino S

    更新日期:2009-02-01 00:00:00

  • Replication of an Autonomous Human Parvovirus in Non-dividing Human Airway Epithelium Is Facilitated through the DNA Damage and Repair Pathways.

    abstract::Human bocavirus 1 (HBoV1) belongs to the genus Bocaparvovirus of the Parvoviridae family, and is an emerging human pathogenic respiratory virus. In vitro, HBoV1 infects well-differentiated/polarized primary human airway epithelium (HAE) cultured at an air-liquid interface (HAE-ALI). Although it is well known that auto...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Deng X,Yan Z,Cheng F,Engelhardt JF,Qiu J

    更新日期:2016-01-14 00:00:00

  • Global Analysis of Mouse Polyomavirus Infection Reveals Dynamic Regulation of Viral and Host Gene Expression and Promiscuous Viral RNA Editing.

    abstract::Mouse polyomavirus (MPyV) lytically infects mouse cells, transforms rat cells in culture, and is highly oncogenic in rodents. We have used deep sequencing to follow MPyV infection of mouse NIH3T6 cells at various times after infection and analyzed both the viral and cellular transcriptomes. Alignment of sequencing rea...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Garren SB,Kondaveeti Y,Duff MO,Carmichael GG

    更新日期:2015-09-25 00:00:00

  • Vector-borne transmission imposes a severe bottleneck on an RNA virus population.

    abstract::RNA viruses typically occur in genetically diverse populations due to their error-prone genome replication. Genetic diversity is thought to be important in allowing RNA viruses to explore sequence space, facilitating adaptation to changing environments and hosts. Some arboviruses that infect both a mosquito vector and...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Forrester NL,Guerbois M,Seymour RL,Spratt H,Weaver SC

    更新日期:2012-09-01 00:00:00

  • Functional Interplay between Type I and II Interferons Is Essential to Limit Influenza A Virus-Induced Tissue Inflammation.

    abstract::Host control of influenza A virus (IAV) is associated with exuberant pulmonary inflammation characterized by the influx of myeloid cells and production of proinflammatory cytokines including interferons (IFNs). It is unclear, however, how the immune system clears the virus without causing lethal immunopathology. Here,...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Stifter SA,Bhattacharyya N,Pillay R,Flórido M,Triccas JA,Britton WJ,Feng CG

    更新日期:2016-01-05 00:00:00

  • Membrane alterations induced by nonstructural proteins of human norovirus.

    abstract::Human noroviruses (huNoV) are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup II genotype 4 (GII.4) variants. The viral nonstructural (NS) proteins encoded by the ORF1 polyprotein induce vesical clusters harboring the viral replication sites. Little is known so far abou...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Doerflinger SY,Cortese M,Romero-Brey I,Menne Z,Tubiana T,Schenk C,White PA,Bartenschlager R,Bressanelli S,Hansman GS,Lohmann V

    更新日期:2017-10-27 00:00:00

  • TLR4 and NKT cell synergy in immunotherapy against visceral leishmaniasis.

    abstract::NKT cells play an important role in autoimmune diseases, tumor surveillance, and infectious diseases, providing in most cases protection against infection. NKT cells are reactive to CD1d presented glycolipid antigens. They can modulate immune responses by promoting the secretion of type 1, type 2, or immune regulatory...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Karmakar S,Bhaumik SK,Paul J,De T

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  • Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague.

    abstract::Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pul...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Vagima Y,Zauberman A,Levy Y,Gur D,Tidhar A,Aftalion M,Shafferman A,Mamroud E

    更新日期:2015-05-14 00:00:00

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

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    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

  • ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response.

    abstract::The retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including RIG-I and melanoma differentiation-associated gene 5 (MDA5), sense cytoplasmic viral RNA and initiate innate antiviral responses. How RIG-I and MDA5 are differentially regulated remains enigmatic. In this study, we identified the guanylate-bin...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Zhong X,Feng L,Zang R,Lei CQ,Yang Q,Shu HB

    更新日期:2020-04-06 00:00:00

  • Disruption of PML nuclear bodies is mediated by ORF61 SUMO-interacting motifs and required for varicella-zoster virus pathogenesis in skin.

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    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Wang L,Oliver SL,Sommer M,Rajamani J,Reichelt M,Arvin AM

    更新日期:2011-08-01 00:00:00

  • PGL I expression in live bacteria allows activation of a CD206/PPARγ cross-talk that may contribute to successful Mycobacterium leprae colonization of peripheral nerves.

    abstract::Mycobacterium leprae, an obligate intracellular bacillus, infects Schwann cells (SCs), leading to peripheral nerve damage, the most severe leprosy symptom. In the present study, we revisited the involvement of phenolic glycolipid I (PGL I), an abundant, private, surface M. leprae molecule, in M. leprae-SC interaction ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Díaz Acosta CC,Dias AA,Rosa TLSA,Batista-Silva LR,Rosa PS,Toledo-Pinto TG,Costa FDMR,Lara FA,Rodrigues LS,Mattos KA,Sarno EN,Bozza PT,Guilhot C,de Berrêdo-Pinho M,Pessolani MCV

    更新日期:2018-07-06 00:00:00

  • A type VII secretion system of Streptococcus gallolyticus subsp. gallolyticus contributes to gut colonization and the development of colon tumors.

    abstract::Streptococcus gallolyticus subspecies gallolyticus (Sgg) has a strong clinical association with colorectal cancer (CRC) and actively promotes the development of colon tumors. However, the molecular determinants involved in Sgg pathogenicity in the gut are unknown. Bacterial type VII secretion systems (T7SS) mediate pa...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Taylor JC,Gao X,Xu J,Holder M,Petrosino J,Kumar R,Liu W,Höök M,Mackenzie C,Hillhouse A,Brashear W,Nunez MP,Xu Y

    更新日期:2021-01-06 00:00:00

  • HIV-1 and M-PMV RNA Nuclear Export Elements Program Viral Genomes for Distinct Cytoplasmic Trafficking Behaviors.

    abstract::Retroviruses encode cis-acting RNA nuclear export elements that override nuclear retention of intron-containing viral mRNAs including the full-length, unspliced genomic RNAs (gRNAs) packaged into assembling virions. The HIV-1 Rev-response element (RRE) recruits the cellular nuclear export receptor CRM1 (also known as ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Pocock GM,Becker JT,Swanson CM,Ahlquist P,Sherer NM

    更新日期:2016-04-12 00:00:00

  • Modulation of the Host Lipid Landscape to Promote RNA Virus Replication: The Picornavirus Encephalomyocarditis Virus Converges on the Pathway Used by Hepatitis C Virus.

    abstract::Cardioviruses, including encephalomyocarditis virus (EMCV) and the human Saffold virus, are small non-enveloped viruses belonging to the Picornaviridae, a large family of positive-sense RNA [(+)RNA] viruses. All (+)RNA viruses remodel intracellular membranes into unique structures for viral genome replication. Accumul...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Dorobantu CM,Albulescu L,Harak C,Feng Q,van Kampen M,Strating JR,Gorbalenya AE,Lohmann V,van der Schaar HM,van Kuppeveld FJ

    更新日期:2015-09-25 00:00:00

  • Determinants of influenza transmission in South East Asia: insights from a household cohort study in Vietnam.

    abstract::To guide control policies, it is important that the determinants of influenza transmission are fully characterized. Such assessment is complex because the risk of influenza infection is multifaceted and depends both on immunity acquired naturally or via vaccination and on the individual level of exposure to influenza ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Cauchemez S,Ferguson NM,Fox A,Mai le Q,Thanh le T,Thai PQ,Thoang DD,Duong TN,Minh Hoa le N,Tran Hien N,Horby P

    更新日期:2014-08-21 00:00:00

  • Tissue Degeneration following Loss of Schistosoma mansoni cbp1 Is Associated with Increased Stem Cell Proliferation and Parasite Death In Vivo.

    abstract::Schistosomiasis is second only to malaria in terms of the global impact among diseases caused by parasites. A striking feature of schistosomes are their ability to thrive in their hosts for decades. We have previously demonstrated that stem cells, called neoblasts, promote homeostatic tissue maintenance in adult schis...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Collins JN,Collins JJ 3rd

    更新日期:2016-11-03 00:00:00

  • mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2.

    abstract::The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic. Critical to the rapid evaluation of vaccines and antivirals against SARS-CoV-2 is the development of tractable animal models to understand the adaptive immune response to the virus. To this end, the use of ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Hassert M,Geerling E,Stone ET,Steffen TL,Feldman MS,Dickson AL,Class J,Richner JM,Brien JD,Pinto AK

    更新日期:2020-12-16 00:00:00

  • Vaccinia virus E3 protein prevents the antiviral action of ISG15.

    abstract::The ubiquitin-like modifier ISG15 is one of the most predominant proteins induced by type I interferons (IFN). In this study, murine embryo fibroblast (MEFs) and mice lacking the gene were used to demonstrate a novel role of ISG15 as a host defense molecule against vaccinia virus (VACV) infection. In MEFs, the growth ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Guerra S,Cáceres A,Knobeloch KP,Horak I,Esteban M

    更新日期:2008-07-04 00:00:00

  • Gene fitness landscapes of Vibrio cholerae at important stages of its life cycle.

    abstract::Vibrio cholerae has evolved to adeptly transition between the human small intestine and aquatic environments, leading to water-borne spread and transmission of the lethal diarrheal disease cholera. Using a host model that mimics the pathology of human cholera, we applied high density transposon mutagenesis combined wi...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Kamp HD,Patimalla-Dipali B,Lazinski DW,Wallace-Gadsden F,Camilli A

    更新日期:2013-01-01 00:00:00

  • Type I J-domain NbMIP1 proteins are required for both Tobacco mosaic virus infection and plant innate immunity.

    abstract::Tm-2² is a coiled coil-nucleotide binding-leucine rich repeat resistance protein that confers durable extreme resistance against Tomato mosaic virus (ToMV) and Tobacco mosaic virus (TMV) by recognizing the viral movement protein (MP). Here we report that the Nicotiana benthamiana J-domain MIP1 proteins (NbMIP1s) assoc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Du Y,Zhao J,Chen T,Liu Q,Zhang H,Wang Y,Hong Y,Xiao F,Zhang L,Shen Q,Liu Y

    更新日期:2013-01-01 00:00:00

  • TGF-beta signaling controls embryo development in the parasitic flatworm Schistosoma mansoni.

    abstract::Over 200 million people have, and another 600 million are at risk of contracting, schistosomiasis, one of the major neglected tropical diseases. Transmission of this infection, which is caused by helminth parasites of the genus Schistosoma, depends upon the release of parasite eggs from the human host. However, approx...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Freitas TC,Jung E,Pearce EJ

    更新日期:2007-04-01 00:00:00

  • A Novel Zn2-Cys6 Transcription Factor AtrR Plays a Key Role in an Azole Resistance Mechanism of Aspergillus fumigatus by Co-regulating cyp51A and cdr1B Expressions.

    abstract::Successful treatment of aspergillosis caused by Aspergillus fumigatus is threatened by an increasing incidence of drug resistance. This situation is further complicated by the finding that strains resistant to azoles, the major antifungal drugs for aspergillosis, have been widely disseminated across the globe. To eluc...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Hagiwara D,Miura D,Shimizu K,Paul S,Ohba A,Gonoi T,Watanabe A,Kamei K,Shintani T,Moye-Rowley WS,Kawamoto S,Gomi K

    更新日期:2017-01-04 00:00:00

  • The novel Candida albicans transporter Dur31 Is a multi-stage pathogenicity factor.

    abstract::Candida albicans is the most frequent cause of oral fungal infections. However, the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized. In this study we sought to functionally characterize 12 previously unknown function ...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Mayer FL,Wilson D,Jacobsen ID,Miramón P,Große K,Hube B

    更新日期:2012-01-01 00:00:00

  • Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and for normal intracellular development of Toxoplasma gondii tachyzoites.

    abstract::Autophagy is a cellular process that is highly conserved among eukaryotes and permits the degradation of cellular material. Autophagy is involved in multiple survival-promoting processes. It not only facilitates the maintenance of cell homeostasis by degrading long-lived proteins and damaged organelles, but it also pl...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Besteiro S,Brooks CF,Striepen B,Dubremetz JF

    更新日期:2011-12-01 00:00:00

  • Utilising animal models to evaluate oseltamivir efficacy against influenza A and B viruses with reduced in vitro susceptibility.

    abstract::The neuraminidase (NA) inhibitor (NAI) oseltamivir (OST) is the most widely used influenza antiviral drug. Several NA amino acid substitutions are reported to reduce viral susceptibility to OST in in vitro assays. However, whether there is a correlation between the level of reduction in susceptibility in vitro and the...

    journal_title:PLoS pathogens

    pub_type: 杂志文章


    authors: Farrukee R,Tai CM,Oh DY,Anderson DE,Gunalan V,Hibberd M,Lau GY,Barr IG,Messling VV,Maurer-Stroh S,Hurt AC

    更新日期:2020-06-18 00:00:00