Petrobactin Is Exported from Bacillus anthracis by the RND-Type Exporter ApeX.

Abstract:

:Bacillus anthracis-a Gram-positive, spore-forming bacterium-causes anthrax, a highly lethal disease with high bacteremia titers. Such rapid growth requires ample access to nutrients, including iron. However, access to this critical metal is heavily restricted in mammals, which requires B. anthracis to employ petrobactin, an iron-scavenging small molecule known as a siderophore. Petrobactin biosynthesis is mediated by asb gene products, and import of the iron-bound (holo)-siderophore into the bacterium has been well studied. In contrast, little is known about the mechanism of petrobactin export following its production in B. anthracis cells. Using a combination of bioinformatics data, gene deletions, and laser ablation electrospray ionization mass spectrometry (LAESI-MS), we identified a resistance-nodulation-cell division (RND)-type transporter, termed ApeX, as a putative petrobactin exporter. Deletion of apeX abrogated export of intact petrobactin, which accumulated inside the cell. However, growth of ΔapeX mutants in iron-depleted medium was not affected, and virulence in mice was not attenuated. Instead, petrobactin components were determined to be exported through a different protein, which enables iron transport sufficient for growth, albeit with a slightly lower affinity for iron. This is the first report to identify a functional siderophore exporter in B. anthracis and the in vivo functionality of siderophore components. Moreover, this is the first application of LAESI-MS to sample a virulence factor/metabolite directly from bacterial culture media and cell pellets of a human pathogen.IMPORTANCEBacillus anthracis requires iron for growth and employs the siderophore petrobactin to scavenge this trace metal during infections. While we understand much about petrobactin biosynthesis and ferric petrobactin import, how apo-petrobactin (iron free) is exported remains unknown. This study used a combination of bioinformatics, genetics, and mass spectrometry to identify the petrobactin exporter. After screening 17 mutants with mutations of candidate exporter genes, we identified the apo-petrobactin exporter (termed ApeX) as a member of the resistance-nodulation-cell division (RND) family of transporters. In the absence of ApeX, petrobactin accumulates inside the cell while continuing to export petrobactin components that are capable of transporting iron. Thus, the loss of ApeX does not affect the ability of B. anthracis to cause disease in mice. This has implications for treatment strategies designed to target and control pathogenicity of B. anthracis in humans.

journal_name

mBio

journal_title

mBio

authors

Hagan AK,Tripathi A,Berger D,Sherman DH,Hanna PC

doi

10.1128/mBio.01238-17

subject

Has Abstract

pub_date

2017-09-12 00:00:00

issue

5

issn

2150-7511

pii

mBio.01238-17

journal_volume

8

pub_type

杂志文章

相关文献

mBio文献大全
  • Decreased, Deformed, Defective-How HIV-1 Vpu Targets Peroxisomes.

    abstract::Peroxisomes are found in essentially all eukaryotic cells and have been described as important hubs in innate sensing and the induction of type III interferons upon viral infection. Nevertheless, it remains poorly investigated how viral pathogens modulate biogenesis or function of peroxisomes to evade innate sensing a...

    journal_title:mBio

    pub_type: 评论,杂志文章

    doi:10.1128/mBio.00967-20

    authors: Hopfensperger K,Sauter D

    更新日期:2020-05-26 00:00:00

  • Functional Characterization of Pneumocystis carinii Inositol Transporter 1.

    abstract::Fungi in the genus Pneumocystis live in the lungs of mammals, where they can cause a fatal pneumonia (PCP [Pneumocystis pneumonia]) in hosts with compromised immune systems. The absence of a continuous in vitro culture system for any species of Pneumocystis has led to limited understanding of these fungi, especially f...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01851-16

    authors: Cushion MT,Collins MS,Sesterhenn T,Porollo A,Vadukoot AK,Merino EJ

    更新日期:2016-12-13 00:00:00

  • Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents.

    abstract::The pharmacopeia used by physicians and laypeople in medieval Europe has largely been dismissed as placebo or superstition. While we now recognize that some of the materia medica used by medieval physicians could have had useful biological properties, research in this area is limited by the labor-intensive process of ...

    journal_title:mBio

    pub_type: 历史文章,杂志文章

    doi:10.1128/mBio.03136-19

    authors: Connelly E,Del Genio CI,Harrison F

    更新日期:2020-02-11 00:00:00

  • Lack of association between the Tlr4 (Lpsd/Lpsd) genotype and increased susceptibility to Escherichia coli bladder infections in female C3H/HeJ mice.

    abstract:UNLABELLED:Toll-like receptor 4 is thought to have a primary role in host defense against Escherichia coli bladder colonization, based on mouse models of urinary tract infection using C3H/HeJ female mice. This strain carries a point mutation in the Tlr4 gene, which renders the mice unresponsive to lipopolysaccharide (L...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00094-11

    authors: Suhs KA,Marthaler BR,Welch RA,Hopkins WJ

    更新日期:2011-05-31 00:00:00

  • Cryo-electron Microscopy Structure of the Acinetobacter baumannii 70S Ribosome and Implications for New Antibiotic Development.

    abstract::Antimicrobial resistance is a major health threat as it limits treatment options for infection. At the forefront of this serious issue is Acinetobacter baumannii, a Gram-negative opportunistic pathogen that exhibits the remarkable ability to resist antibiotics through multiple mechanisms. As bacterial ribosomes repres...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.03117-19

    authors: Morgan CE,Huang W,Rudin SD,Taylor DJ,Kirby JE,Bonomo RA,Yu EW

    更新日期:2020-01-21 00:00:00

  • Clinical characteristics and outcomes of prosthetic joint infection caused by small colony variant staphylococci.

    abstract:UNLABELLED:Small colony variants (SCVs) are naturally occurring subpopulations of bacteria. The clinical characteristics and treatment outcomes of patients with prosthetic joint infection (PJI) caused by staphylococcal SCVs are unknown. This study was a retrospective series of 113 patients with staphylococcal PJI, with...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01910-14

    authors: Tande AJ,Osmon DR,Greenwood-Quaintance KE,Mabry TM,Hanssen AD,Patel R

    更新日期:2014-09-30 00:00:00

  • Identification of a gamma interferon-activated inhibitor of translation-like RNA motif at the 3' end of the transmissible gastroenteritis coronavirus genome modulating innate immune response.

    abstract:UNLABELLED:A 32-nucleotide (nt) RNA motif located at the 3' end of the transmissible gastroenteritis coronavirus (TGEV) genome was found to specifically interact with the host proteins glutamyl-prolyl-tRNA synthetase (EPRS) and arginyl-tRNA synthetase (RRS). This RNA motif has high homology in sequence and secondary st...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00105-15

    authors: Marquez-Jurado S,Nogales A,Zuñiga S,Enjuanes L,Almazán F

    更新日期:2015-03-10 00:00:00

  • The Bacterium Frischella perrara Causes Scab Formation in the Gut of its Honeybee Host.

    abstract:UNLABELLED:Honeybees harbor well-defined bacterial communities in their guts. The major members of these communities appear to benefit the host, but little is known about how they interact with the host and specifically how they interface with the host immune system. In the pylorus, a short region between the midgut an...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00193-15

    authors: Engel P,Bartlett KD,Moran NA

    更新日期:2015-05-19 00:00:00

  • Pseudomonas biofilms, cystic fibrosis, and phage: a silver lining?

    abstract::In contrast to usual laboratory conditions, most bacteria in the human body grow in biofilms. Encased in a structured matrix, many pathogens display heightened resistance to antibiotics. Pseudomonas aeruginosa lung infections in cystic fibrosis patients represent a prime example of the clinical challenges that antibio...

    journal_title:mBio

    pub_type: 评论,杂志文章

    doi:10.1128/mBio.00061-12

    authors: Brüssow H

    更新日期:2012-04-03 00:00:00

  • Phyllosphere microbiota composition and microbial community transplantation on lettuce plants grown indoors.

    abstract:UNLABELLED:The aerial surfaces of plants, or phyllosphere, are microbial habitats important to plant and human health. In order to accurately investigate microbial interactions in the phyllosphere under laboratory conditions, the composition of the phyllosphere microbiota should be representative of the diversity of mi...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01564-14

    authors: Williams TR,Marco ML

    更新日期:2014-08-12 00:00:00

  • Novel (p)ppGpp Binding and Metabolizing Proteins of Escherichia coli.

    abstract::The alarmone (p)ppGpp plays pivotal roles in basic bacterial stress responses by increasing tolerance of various nutritional limitations and chemical insults, including antibiotics. Despite intensive studies since (p)ppGpp was discovered over 4 decades ago, (p)ppGpp binding proteins have not been systematically identi...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02188-17

    authors: Zhang Y,Zborníková E,Rejman D,Gerdes K

    更新日期:2018-03-06 00:00:00

  • Offloading Role of a Discrete Thioesterase in Type II Polyketide Biosynthesis.

    abstract::Type II polyketides are a group of secondary metabolites with various biological activities. In nature, biosynthesis of type II polyketides involves multiple enzymatic steps whereby key enzymes, including ketoacyl-synthase (KSα), chain length factor (KSβ), and acyl carrier protein (ACP), are utilized to elongate the p...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01334-20

    authors: Hua K,Liu X,Zhao Y,Gao Y,Pan L,Zhang H,Deng Z,Jiang M

    更新日期:2020-09-15 00:00:00

  • Sleeping Beauty and the Story of the Bacille Calmette-Guérin Vaccine.

    abstract::Mycobacterium bovis BCG is the only available vaccine for protection against tuberculosis (TB). While BCG protects children from severe disease, it has little impact on pulmonary disease in adults. A recombinant BCG vaccine BCG ΔureC::hly (strain VPM1002) is in advanced clinical trials and shows promise for improved v...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01370-16

    authors: Fletcher HA

    更新日期:2016-08-30 00:00:00

  • Streptococcus pneumoniae is desiccation tolerant and infectious upon rehydration.

    abstract:UNLABELLED:Streptococcus pneumoniae (pneumococcus) is a frequent colonizer of the nasopharynx and one of the leading causative agents of otitis media, pneumonia, and meningitis. The current literature asserts that S. pneumoniae is transmitted person to person via respiratory droplets; however, environmental surfaces (f...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00092-11

    authors: Walsh RL,Camilli A

    更新日期:2011-05-24 00:00:00

  • Viral Diversity of House Mice in New York City.

    abstract::The microbiome of wild Mus musculus (house mouse), a globally distributed invasive pest that resides in close contact with humans in urban centers, is largely unexplored. Here, we report analysis of the fecal virome of house mice in residential buildings in New York City, NY. Mice were collected at seven sites in Manh...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01354-17

    authors: Williams SH,Che X,Garcia JA,Klena JD,Lee B,Muller D,Ulrich W,Corrigan RM,Nichol S,Jain K,Lipkin WI

    更新日期:2018-04-17 00:00:00

  • Population Structure and Genetic Diversity among Isolates of Coccidioides posadasii in Venezuela and Surrounding Regions.

    abstract::Coccidioides posadasii is a pathogenic fungus that causes coccidioidomycosis in many arid regions of the Americas. One of these regions is bordered by the Caribbean Sea, and the surrounding landscape may play an important role in the dispersion of C. posadasii across South America through southeastern Mexico, Honduras...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01976-19

    authors: Teixeira MM,Alvarado P,Roe CC,Thompson GR 3rd,Patané JSL,Sahl JW,Keim P,Galgiani JN,Litvintseva AP,Matute DR,Barker BM

    更新日期:2019-11-26 00:00:00

  • A Key Motif in the Cholesterol-Dependent Cytolysins Reveals a Large Family of Related Proteins.

    abstract::The cholesterol-dependent cytolysins (CDCs) are bacterial, β-barrel, pore-forming toxins. A central enigma of the pore-forming mechanism is how completion of the prepore is sensed to initiate its conversion to the pore. We identified a motif that is conserved between the CDCs and a diverse family of nearly 300 unchara...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02351-20

    authors: Evans JC,Johnstone BA,Lawrence SL,Morton CJ,Christie MP,Parker MW,Tweten RK

    更新日期:2020-09-29 00:00:00

  • Designing the Next Generation of Vaccines: Relevance for Future Pandemics.

    abstract::The development of vaccines is one of the greatest medical interventions in the history of global infectious diseases and has contributed to the annual saving of at least 2 to 3 million lives worldwide. However, many diseases are not preventable through currently available vaccines, and the potential of modulating the...

    journal_title:mBio

    pub_type: 杂志文章,评审

    doi:10.1128/mBio.02616-20

    authors: Domínguez-Andrés J,van Crevel R,Divangahi M,Netea MG

    更新日期:2020-12-22 00:00:00

  • Aspergillus fumigatus Transcription Factors Involved in the Caspofungin Paradoxical Effect.

    abstract::Aspergillus fumigatus is the leading cause of pulmonary fungal diseases. Azoles have been used for many years as the main antifungal agents to treat and prevent invasive aspergillosis. However, in the last 10 years there have been several reports of azole resistance in A. fumigatus and new strategies are needed to com...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00816-20

    authors: Valero C,Colabardini AC,Chiaratto J,Pardeshi L,de Castro PA,Ferreira Filho JA,Silva LP,Rocha MC,Malavazi I,Costa JH,Fill T,Barros MH,Wong SSW,Aimanianda V,Wong KH,Goldman GH

    更新日期:2020-06-16 00:00:00

  • Multiple Histone Lysine Methyltransferases Are Required for the Establishment and Maintenance of HIV-1 Latency.

    abstract::We showed previously that the histone lysine methyltransferase (HKMT) H3K27me3 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and is required for the maintenance of HIV-1 latency in Jurkat T cells. Here we show, by using chromatin immunoprecipitation experiments, that both PRC2 and euchromatic...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00133-17

    authors: Nguyen K,Das B,Dobrowolski C,Karn J

    更新日期:2017-02-28 00:00:00

  • Cuts Both Ways: Proteases Modulate Virulence of Enterohemorrhagic Escherichia coli.

    abstract::Enterohemorrhagic Escherichia coli (EHEC) is a major cause of foodborne gastrointestinal illness. EHEC uses a specialized type III secretion system (T3SS) to form attaching and effacing lesions in the colonic epithelium and outcompete commensal gut microbiota to cause disease. A recent report in mBio (E. A. Cameron, M...

    journal_title:mBio

    pub_type: 评论,杂志文章

    doi:10.1128/mBio.00115-19

    authors: Palmer LD,Skaar EP

    更新日期:2019-02-26 00:00:00

  • Human claudin-8 and -14 are receptors capable of conveying the cytotoxic effects of Clostridium perfringens enterotoxin.

    abstract:UNLABELLED:Clostridium perfringens enterotoxin (CPE) contributes to several important human gastrointestinal (GI) diseases. This toxin and its derivatives are also being explored for translational applications, i.e., cancer therapy or drug delivery. Some, but not all, members of the 24-member claudin (Cldn) family of m...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00594-12

    authors: Shrestha A,McClane BA

    更新日期:2013-01-15 00:00:00

  • Integration of the second messenger c-di-GMP into the chemotactic signaling pathway.

    abstract:UNLABELLED:Elevated intracellular levels of the bacterial second messenger c-di-GMP are known to suppress motility and promote sessility. Bacterial chemotaxis guides motile cells in gradients of attractants and repellents over broad concentration ranges, thus allowing bacteria to quickly adapt to changes in their surro...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00001-13

    authors: Russell MH,Bible AN,Fang X,Gooding JR,Campagna SR,Gomelsky M,Alexandre G

    更新日期:2013-03-19 00:00:00

  • Chromosomal "stress-response" domains govern the spatiotemporal expression of the bacterial virulence program.

    abstract:UNLABELLED:Recent studies strongly suggest that the gene expression sustaining both normal and pathogenic bacterial growth is governed by the structural dynamics of the chromosome. However, the mechanistic device coordinating the chromosomal configuration with selective expression of the adaptive traits remains largely...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00353-15

    authors: Jiang X,Sobetzko P,Nasser W,Reverchon S,Muskhelishvili G

    更新日期:2015-04-28 00:00:00

  • Topological Analysis of the Type 3 Secretion System Translocon Pore Protein IpaC following Its Native Delivery to the Plasma Membrane during Infection.

    abstract::Many Gram-negative bacterial pathogens require a type 3 secretion system (T3SS) to deliver effector proteins into eukaryotic cells. Contact of the tip complex of the T3SS with a target eukaryotic cell initiates secretion of the two bacterial proteins that assemble into the translocon pore in the plasma membrane. The t...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00877-19

    authors: Russo BC,Duncan JK,Goldberg MB

    更新日期:2019-05-28 00:00:00

  • RadD Contributes to R-Loop Avoidance in Sub-MIC Tobramycin.

    abstract::We have previously identified Vibrio cholerae mutants in which the stress response to subinhibitory concentrations of aminoglycoside is altered. One gene identified, VC1636, encodes a putative DNA/RNA helicase, recently named RadD in Escherichia coli Here we combined extensive genetic characterization and high-through...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01173-19

    authors: Negro V,Krin E,Aguilar Pierlé S,Chaze T,Giai Gianetto Q,Kennedy SP,Matondo M,Mazel D,Baharoglu Z

    更新日期:2019-07-02 00:00:00

  • The Yeast PCNA Unloader Elg1 RFC-Like Complex Plays a Role in Eliciting the DNA Damage Checkpoint.

    abstract::The PCNA (proliferating cell nuclear antigen) ring plays central roles during DNA replication and repair. The yeast Elg1 RFC-like complex (RLC) is the principal unloader of chromatin-bound PCNA and thus plays a central role in maintaining genome stability. Here we identify a role for Elg1 in the unloading of PCNA duri...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.01159-19

    authors: Sau S,Liefshitz B,Kupiec M

    更新日期:2019-06-11 00:00:00

  • Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance.

    abstract::The hospital environment is a potential reservoir of bacteria with plasmids conferring carbapenem resistance. Our Hospital Epidemiology Service routinely performs extensive sampling of high-touch surfaces, sinks, and other locations in the hospital. Over a 2-year period, additional sampling was conducted at a broader ...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.02011-17

    authors: Weingarten RA,Johnson RC,Conlan S,Ramsburg AM,Dekker JP,Lau AF,Khil P,Odom RT,Deming C,Park M,Thomas PJ,NISC Comparative Sequencing Program.,Henderson DK,Palmore TN,Segre JA,Frank KM

    更新日期:2018-02-06 00:00:00

  • Heteroresistance at the single-cell level: adapting to antibiotic stress through a population-based strategy and growth-controlled interphenotypic coordination.

    abstract:UNLABELLED:Heteroresistance refers to phenotypic heterogeneity of microbial clonal populations under antibiotic stress, and it has been thought to be an allocation of a subset of "resistant" cells for surviving in higher concentrations of antibiotic. The assumption fits the so-called bet-hedging strategy, where a bacte...

    journal_title:mBio

    pub_type: 杂志文章,多中心研究

    doi:10.1128/mBio.00942-13

    authors: Wang X,Kang Y,Luo C,Zhao T,Liu L,Jiang X,Fu R,An S,Chen J,Jiang N,Ren L,Wang Q,Baillie JK,Gao Z,Yu J

    更新日期:2014-02-11 00:00:00

  • Sensing of bacterial type IV secretion via the unfolded protein response.

    abstract::Host cytokine responses to Brucella abortus infection are elicited predominantly by the deployment of a type IV secretion system (T4SS). However, the mechanism by which the T4SS elicits inflammation remains unknown. Here we show that translocation of the T4SS substrate VceC into host cells induces proinflammatory resp...

    journal_title:mBio

    pub_type: 杂志文章

    doi:10.1128/mBio.00418-12

    authors: de Jong MF,Starr T,Winter MG,den Hartigh AB,Child R,Knodler LA,van Dijl JM,Celli J,Tsolis RM

    更新日期:2013-02-19 00:00:00