The metabolic regulator CodY links Listeria monocytogenes metabolism to virulence by directly activating the virulence regulatory gene prfA.

Abstract:

:Metabolic adaptations are critical to the ability of bacterial pathogens to grow within host cells and are normally preceded by sensing of host-specific metabolic signals, which in turn can influence the pathogen's virulence state. Previously, we reported that the intracellular bacterial pathogen Listeria monocytogenes responds to low availability of branched-chain amino acids (BCAAs) within mammalian cells by up-regulating both BCAA biosynthesis and virulence genes. The induction of virulence genes required the BCAA-responsive transcription regulator, CodY, but the molecular mechanism governing this mode of regulation was unclear. In this report, we demonstrate that CodY directly binds the coding sequence of the L. monocytogenes master virulence activator gene, prfA, 15 nt downstream of its start codon, and that this binding results in up-regulation of prfA transcription specifically under low concentrations of BCAA. Mutating this site abolished CodY binding and reduced prfA transcription in macrophages, and attenuated bacterial virulence in mice. Notably, the mutated binding site did not alter prfA transcription or PrfA activity under other conditions that are known to activate PrfA, such as during growth in the presence of glucose-1-phosphate. This study highlights the tight crosstalk between L. monocytogenes metabolism and virulence, while revealing novel features of CodY-mediated regulation.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Lobel L,Sigal N,Borovok I,Belitsky BR,Sonenshein AL,Herskovits AA

doi

10.1111/mmi.12890

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

624-44

issue

4

eissn

0950-382X

issn

1365-2958

journal_volume

95

pub_type

杂志文章
  • Enzymes involved in plastid-targeted phosphatidic acid synthesis are essential for Plasmodium yoelii liver-stage development.

    abstract::Malaria parasites scavenge nutrients from their host but also harbour enzymatic pathways for de novo macromolecule synthesis. One such pathway is apicoplast-targeted type II fatty acid synthesis, which is essential for late liver-stage development in rodent malaria. It is likely that fatty acids synthesized in the api...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12485

    authors: Lindner SE,Sartain MJ,Hayes K,Harupa A,Moritz RL,Kappe SH,Vaughan AM

    更新日期:2014-02-01 00:00:00

  • The MreB and Min cytoskeletal-like systems play independent roles in prokaryotic polar differentiation.

    abstract::Establishment of an axis of cell polarity and differentiation of the cell poles are fundamental aspects of cellular development in many organisms. We compared the effects of two bacterial cytoskeletal-like systems, the MreB and MinCDE systems, on these processes in Escherichia coli. We report that the Min proteins are...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04841.x

    authors: Shih YL,Kawagishi I,Rothfield L

    更新日期:2005-11-01 00:00:00

  • An Agrobacterium two-component regulatory system for the detection of chemicals released from plant wounds.

    abstract::Crown gall tumorigenesis by Agrobacterium tumefaciens requires the co-ordinate transcriptional induction of a set of pathogenesis genes. At least three classes of environmental stimuli act synergistically to induce these genes: (i) monocyclic aromatic hydrocarbons such as acetosyringone, coniferyl alcohol, and vanilli...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2958.1991.tb02080.x

    authors: Winans SC

    更新日期:1991-10-01 00:00:00

  • Disruption of msl3 abolishes the synthesis of mycolipanoic and mycolipenic acids required for polyacyltrehalose synthesis in Mycobacterium tuberculosis H37Rv and causes cell aggregation.

    abstract::Cell wall lipids of Mycobacterium tuberculosis containing multiple methylbranched fatty acids play critical roles in pathogenesis and thus offer targets for new antimycobacterial drugs. Mycocerosicacid synthase gene (mas) encodes the enzyme that produces one class of such acids. Seven mas-like genes (msls) were identi...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.03119.x

    authors: Dubey VS,Sirakova TD,Kolattukudy PE

    更新日期:2002-09-01 00:00:00

  • nasST, two genes involved in the induction of the assimilatory nitrite-nitrate reductase operon (nasAB) of Azotobacter vinelandii.

    abstract::An operon including two new genes (nasS and nasT) has been defined, cloned and sequenced. The deduced NASS protein is homologous to NRTA from Synechococcus sp. and to NASF from Klebsiella pneumoniae, two proteins involved in nitrate uptake. The predicted NAST polypeptide is homologous to the regulator proteins of the ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1995.mmi_18030579.x

    authors: Gutierrez JC,Ramos F,Ortner L,Tortolero M

    更新日期:1995-11-01 00:00:00

  • Biochemical characterization of a Neisseria meningitidis polysialyltransferase reveals novel functional motifs in bacterial sialyltransferases.

    abstract::The extracellular polysaccharide capsule is an essential virulence factor of Neisseria meningitidis, a leading cause of severe bacterial meningitis and sepsis. Serogroup B strains, the primary disease causing isolates in Europe and America, are encapsulated in alpha-2,8 polysialic acid (polySia). The capsular polymer ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2007.05862.x

    authors: Freiberger F,Claus H,Günzel A,Oltmann-Norden I,Vionnet J,Mühlenhoff M,Vogel U,Vann WF,Gerardy-Schahn R,Stummeyer K

    更新日期:2007-09-01 00:00:00

  • McmA-dependent and -independent regulatory systems governing expression of ClrB-regulated cellulase and hemicellulase genes in Aspergillus nidulans.

    abstract::Fungal cellulolytic and hemicellulolytic enzymes are promising tools for industrial hydrolysis of cellulosic biomass; however, the regulatory network underlying their production is not well understood. The recent discovery of the transcriptional activators ClrB and McmA in Aspergillus nidulans implied a novel regulato...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13493

    authors: Li N,Kunitake E,Aoyama M,Ogawa M,Kanamaru K,Kimura M,Koyama Y,Kobayashi T

    更新日期:2016-12-01 00:00:00

  • Phase variation of HpuAB and HmbR, two distinct haemoglobin receptors of Neisseria meningitidis DNM2.

    abstract::We have previously described HpuAB, a two-component receptor that mediates binding to haemoglobin (Hb), haemoglobin-haptoglobin (Hb-Hp) and apo-haptoglobin (Hp). In this communication, we constructed non-polar mutations in the hpuA and hpuB loci to examine the individual roles of HpuA and HpuB. Our results indicate th...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01409.x

    authors: Lewis LA,Gipson M,Hartman K,Ownbey T,Vaughn J,Dyer DW

    更新日期:1999-06-01 00:00:00

  • Aminoacyl-tRNA synthesis in archaea: different but not unique.

    abstract::Accurate aminoacyl-tRNA synthesis is essential for correct translation of the genetic code in all organisms. Whereas many aspects of this process are conserved, others display a surprisingly high level of divergence from the canonical Escherichia coli model system. These differences are most pronounced in archaea wher...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1046/j.1365-2958.2003.03330.x

    authors: Praetorius-Ibba M,Ibba M

    更新日期:2003-05-01 00:00:00

  • Identification and characterization of genes encoding sex pheromone cAM373 activity in Enterococcus faecalis and Staphylococcus aureus.

    abstract::The sex pheromone cAM373 of Enterococcus faecalis and the related staph-cAM373 of Staphylococcus aureus were found to correspond to heptapeptides located within the C-termini of the signal sequences of putative prelipoproteins. The deduced mature forms of the lipoproteins share no detectable homology and presumably se...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.02922.x

    authors: Flannagan SE,Clewell DB

    更新日期:2002-05-01 00:00:00

  • Cloning, sequencing and deletion from the chromosome of the gene encoding subunit I of the aa3-type cytochrome c oxidase of Rhodobacter sphaeroides.

    abstract::The ctaD gene encoding subunit I of the aa3-type cytochrome c oxidase from Rhodobacter sphaeroides has been cloned. The gene encodes a polypeptide of 565 residues which is highly homologous to the sequences of subunit I from other prokaryotic and eukaryotic sources, e.g. 51% identity with that from bovine, and 75% ide...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1992.tb01511.x

    authors: Shapleigh JP,Gennis RB

    更新日期:1992-03-01 00:00:00

  • The power of cooperation: Experimental and computational approaches in the functional characterization of bacterial sRNAs.

    abstract::Trans-acting small regulatory RNAs (sRNAs) are key players in the regulation of gene expression in bacteria. There are hundreds of different sRNAs in a typical bacterium, which in contrast to eukaryotic microRNAs are more heterogeneous in length, sequence composition, and secondary structure. The vast majority of sRNA...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/mmi.14420

    authors: Georg J,Lalaouna D,Hou S,Lott SC,Caldelari I,Marzi S,Hess WR,Romby P

    更新日期:2020-03-01 00:00:00

  • Human pregnancy-associated malaria-specific B cells target polymorphic, conformational epitopes in VAR2CSA.

    abstract::Pregnancy-associated malaria (PAM) is caused by Plasmodium falciparum-infected erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta by PAM-associated clonally variant surface antigens (VSA). Pregnancy-specific VSA (VSA(PAM)), which include the PfEMP1 variant VAR2CSA, are targets of IgG-mediated...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2006.05503.x

    authors: Barfod L,Bernasconi NL,Dahlbäck M,Jarrossay D,Andersen PH,Salanti A,Ofori MF,Turner L,Resende M,Nielsen MA,Theander TG,Sallusto F,Lanzavecchia A,Hviid L

    更新日期:2007-01-01 00:00:00

  • Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcgammaRIIa receptor.

    abstract::Staphylococcus aureus is a leading cause of infective endocarditis (IE). Platelet activation promoted by S. aureus resulting in aggregation and thrombus formation is an important step in the pathogenesis of IE. Here, we report that the fibrinogen/fibronectin-binding proteins FnBPA and FnBPB are major platelet-activati...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2005.04922.x

    authors: Fitzgerald JR,Loughman A,Keane F,Brennan M,Knobel M,Higgins J,Visai L,Speziale P,Cox D,Foster TJ

    更新日期:2006-01-01 00:00:00

  • Recombination of synthetic oligonucleotides with prokaryotic chromosomes: substrate requirements of the Escherichia coli/lambdaRed and Sulfolobus acidocaldarius recombination systems.

    abstract::In order to reveal functional properties of recombination involving short ssDNAs in hyperthermophilic archaea, we evaluated oligonucleotide-mediated transformation (OMT) in Sulfolobus acidocaldarius and Escherichia coli as a function of the molecular properties of the ssDNA substrates. Unmodified ssDNAs as short as 20...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2008.06356.x

    authors: Grogan DW,Stengel KR

    更新日期:2008-09-01 00:00:00

  • Involvement of an X family DNA polymerase in double-stranded break repair in the radioresistant organism Deinococcus radiodurans.

    abstract::DNA polymerases of the X family have been implicated in a variety of DNA repair processes in eukaryotes. Here we show that Deinococcus radiodurans, a highly radioresistant bacterium able to mend hundreds of radiation-induced double-stranded DNA breaks, expresses a DNA polymerase belonging to the X family. This novel b...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2004.04233.x

    authors: Lecointe F,Shevelev IV,Bailone A,Sommer S,Hübscher U

    更新日期:2004-09-01 00:00:00

  • Multiple roles of Pseudomonas aeruginosa TBCF10839 PilY1 in motility, transport and infection.

    abstract::Polymorphonuclear neutrophils are the most important mammalian host defence cells against infections with Pseudomonas aeruginosa. Screening of a signature tagged mutagenesis library of the non-piliated P. aeruginosa strain TBCF10839 uncovered that transposon inactivation of its pilY1 gene rendered the bacterium more r...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2008.06559.x

    authors: Bohn YS,Brandes G,Rakhimova E,Horatzek S,Salunkhe P,Munder A,van Barneveld A,Jordan D,Bredenbruch F,Häussler S,Riedel K,Eberl L,Jensen PØ,Bjarnsholt T,Moser C,Hoiby N,Tümmler B,Wiehlmann L

    更新日期:2009-02-01 00:00:00

  • Characterization of FapR, a positive regulator of expression of the 987P operon in enterotoxigenic Escherichia coli.

    abstract::Expression of the 987P gene cluster is activated by the adjacent IS1 element of an STpa transposon. Nucleotide sequence analysis of the 987P-DNA region contiguous with this IS1 element revealed the presence of an open reading frame designated fapR, encoding a basic protein of 260 amino acid residues with a molecular m...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1990.tb00556.x

    authors: Klaasen P,de Graaf FK

    更新日期:1990-10-01 00:00:00

  • Involvement of multiple DNA elements in iron-inducible transcription of the ap65-1 gene in the protozoan parasite Trichomonas vaginalis.

    abstract::A reputed iron-responsive region, which contains multiple nuclear protein-binding DNA sequences, was shown previously to regulate iron-inducible transcription of the ap65-1 gene in the protozoan pathogen, Trichomonas vaginalis. These DNA sequences include two overlapping MYB recognition elements (MRE-1/MRE-2r) and thr...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2004.04088.x

    authors: Ong SJ,Huang SC,Liu HW,Tai JH

    更新日期:2004-06-01 00:00:00

  • Rearrangements in the staphylococcal beta-lactamase-encoding plasmid, pIP1066, including a DNA inversion that generates two alternative transposons.

    abstract::The plasmid plP1066, harboured by by a methicillin-resistant Staphylococcus aureus strain isolated in France, carries genes specifying beta-lactamase. This plasmid undergoes numerous rearrangements. One of these was insertion, between the genes binR and sin encoding resolvases, of a 16 kb element which displayed the c...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1995.mmi_17040769.x

    authors: Derbise A,Dyke KG,el Solh N

    更新日期:1995-08-01 00:00:00

  • The transmembrane domains of the sensor kinase KdpD of Escherichia coli are not essential for sensing K+ limitation.

    abstract::The sensor kinase/response regulator system KdpD/KdpE of Escherichia coli regulates the expression of the kdpFABC operon, which encodes the high affinity K+ transport system KdpFABC. The membrane-bound sensor kinase KdpD consists of four transmembrane domains, a large cytoplasmic N-terminal domain and a cytoplasmic C-...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03348.x

    authors: Heermann R,Fohrmann A,Altendorf K,Jung K

    更新日期:2003-02-01 00:00:00

  • CheY's acetylation sites responsible for generating clockwise flagellar rotation in Escherichia coli.

    abstract::Stimulation of Escherichia coli with acetate elevates the acetylation level of the chemotaxis response regulator CheY. This elevation, in an unknown mechanism, activates CheY to generate clockwise rotation. Here, using quantitative selective reaction monitoring mass spectrometry and high-resolution targeted mass spect...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12858

    authors: Fraiberg M,Afanzar O,Cassidy CK,Gabashvili A,Schulten K,Levin Y,Eisenbach M

    更新日期:2015-01-01 00:00:00

  • Protected environments allow parallel evolution of a bacterial pathogen in a patient subjected to long-term antibiotic therapy.

    abstract::Long-term antibiotic treatment offers a rare opportunity to study the evolution of bacteria within the same individual. The appearance of new variants has been suggested to take place via the selection of enhanced resistance in compartments of the body in which the antibiotic concentration is low. Laboratory models of...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2001.02647.x

    authors: Low AS,MacKenzie FM,Gould IM,Booth IR

    更新日期:2001-11-01 00:00:00

  • Tn5 transposase loops DNA in the absence of Tn5 transposon end sequences.

    abstract::Transposases mediate transposition first by binding specific DNA end sequences that define a transposable element and then by organizing protein and DNA into a highly structured and stable nucleoprotein 'synaptic' complex. Synaptic complex assembly is a central checkpoint in many transposition mechanisms. The Tn5 syna...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2006.05471.x

    authors: Adams CD,Schnurr B,Skoko D,Marko JF,Reznikoff WS

    更新日期:2006-12-01 00:00:00

  • Reversible topology of a bifunctional transmembrane protein depends upon the charge balance around its transmembrane domain.

    abstract::Hybrid genes were constructed to express bifunctional hybrid proteins in which staphyloccal nuclease A with or without an amino-terminal OmpA signal sequence was fused with TEM beta-lactamase (at the carboxyl terminal side) using the signal peptide of the major outer membrane lipoprotein of Escherichia coli as an inte...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb00360.x

    authors: Kim H,Paul S,Gennity J,Jennity J corrected to Gennity J,Inouye M

    更新日期:1994-03-01 00:00:00

  • Clostridium difficile toxin expression is inhibited by the novel regulator TcdC.

    abstract::Clostridium difficile, an emerging nosocomial pathogen of increasing clinical significance, produces two large protein toxins that are responsible for the cellular damage associated with the disease. The precise mechanisms by which toxin synthesis is regulated in response to environmental change have yet to be discove...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2007.05739.x

    authors: Matamouros S,England P,Dupuy B

    更新日期:2007-06-01 00:00:00

  • The molecular characterization of the first autolytic lysozyme of Streptococcus pneumoniae reveals evolutionary mobile domains.

    abstract::A biochemical approach to identify proteins with high affinity for choline-containing pneumococcal cell walls has allowed the localization, cloning and sequencing of a gene (lytC ) coding for a protein that degrades the cell walls of Streptococcus pneumoniae. The lytC gene is 1506 bp long and encodes a protein (LytC) ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01455.x

    authors: García P,Paz González M,García E,García JL,López R

    更新日期:1999-07-01 00:00:00

  • Deletion analysis resolves cell-binding and lytic domains of the Pasteurella leukotoxin.

    abstract::A series of internal deletions in the lktA gene of Pasteurella haemolytica has been constructed. All of the deletions eliminated the lytic activity of the leukotoxin towards the bovine lymphoma cell line, BL-3. Deletions removing segments of the amino-proximal hydrophobic region, which is thought to constitute an esse...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1990.tb02042.x

    authors: Cruz WT,Young R,Chang YF,Struck DK

    更新日期:1990-11-01 00:00:00

  • Characterization of integration host factor (IHF) binding upstream of the cysteine-rich protein operon (omcAB) promoter of Chlamydia trachomatis LGV serovar L2.

    abstract::Chlamydiae are bacterial parasites that carry out a distinct developmental cycle within host cells; however, the mechanisms by which these organisms regulate stage-specific gene expression are not known. We identified a DNA element located between nucleotide (nt) -135 and -90 upstream from the transcription start poin...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2001.02531.x

    authors: Zhong J,Douglas AL,Hatch TP

    更新日期:2001-07-01 00:00:00

  • Assembly of the translocase motor onto the preprotein-conducting channel.

    abstract::Bacterial protein secretion is catalysed by the SecYEG protein-conducting channel complexed with the SecA ATPase motor. To gain insight into the SecA-SecYEG interaction we used peptide arrays, thermodynamic quantification, mutagenesis and functional assays. Our data reveal that: (i) SecA binds with low affinity on sev...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2008.06402.x

    authors: Karamanou S,Bariami V,Papanikou E,Kalodimos CG,Economou A

    更新日期:2008-10-01 00:00:00