Toxin Kid uncouples DNA replication and cell division to enforce retention of plasmid R1 in Escherichia coli cells.

Abstract:

:Worldwide dissemination of antibiotic resistance in bacteria is facilitated by plasmids that encode postsegregational killing (PSK) systems. These produce a stable toxin (T) and a labile antitoxin (A) conditioning cell survival to plasmid maintenance, because only this ensures neutralization of toxicity. Shortage of antibiotic alternatives and the link of TA pairs to PSK have stimulated the opinion that premature toxin activation could be used to kill these recalcitrant organisms in the clinic. However, validation of TA pairs as therapeutic targets requires unambiguous understanding of their mode of action, consequences for cell viability, and function in plasmids. Conflicting with widespread notions concerning these issues, we had proposed that the TA pair kis-kid (killing suppressor-killing determinant) might function as a plasmid rescue system and not as a PSK system, but this remained to be validated. Here, we aimed to clarify unsettled mechanistic aspects of Kid activation, and of the effects of this for kis-kid-bearing plasmids and their host cells. We confirm that activation of Kid occurs in cells that are about to lose the toxin-encoding plasmid, and we show that this provokes highly selective restriction of protein outputs that inhibits cell division temporarily, avoiding plasmid loss, and stimulates DNA replication, promoting plasmid rescue. Kis and Kid are conserved in plasmids encoding multiple antibiotic resistance genes, including extended spectrum β-lactamases, for which therapeutic options are scarce, and our findings advise against the activation of this TA pair to fight pathogens carrying these extrachromosomal DNAs.

authors

Pimentel B,Nair R,Bermejo-Rodríguez C,Preston MA,Agu CA,Wang X,Bernal JA,Sherratt DJ,de la Cueva-Méndez G

doi

10.1073/pnas.1308241111

subject

Has Abstract

pub_date

2014-02-18 00:00:00

pages

2734-9

issue

7

eissn

0027-8424

issn

1091-6490

pii

1308241111

journal_volume

111

pub_type

杂志文章
  • The Arabidopsis SOS2 protein kinase physically interacts with and is activated by the calcium-binding protein SOS3.

    abstract::The Arabidopsis thaliana SOS2 and SOS3 genes are required for intracellular Na(+) and K(+) homeostasis and plant tolerance to high Na(+) and low K(+) environments. SOS3 is an EF hand type calcium-binding protein having sequence similarities with animal neuronal calcium sensors and the yeast calcineurin B. SOS2 is a se...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.040577697

    authors: Halfter U,Ishitani M,Zhu JK

    更新日期:2000-03-28 00:00:00

  • A long-range regulatory element of Hoxc8 identified by using the pClasper vector.

    abstract::Hox genes are located in highly conserved clusters. The significance of this organization is unclear, but one possibility is that regulatory regions for individual genes are dispersed throughout the cluster and shared with other Hox genes. This hypothesis is supported by studies on several Hox genes in which even larg...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.6.2426

    authors: Bradshaw MS,Shashikant CS,Belting HG,Bollekens JA,Ruddle FH

    更新日期:1996-03-19 00:00:00

  • Structural basis for gating mechanisms of a eukaryotic P-glycoprotein homolog.

    abstract::P-glycoprotein is an ATP-binding cassette multidrug transporter that actively transports chemically diverse substrates across the lipid bilayer. The precise molecular mechanism underlying transport is not fully understood. Here, we present crystal structures of a eukaryotic P-glycoprotein homolog, CmABCB1 from Cyanidi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1321562111

    authors: Kodan A,Yamaguchi T,Nakatsu T,Sakiyama K,Hipolito CJ,Fujioka A,Hirokane R,Ikeguchi K,Watanabe B,Hiratake J,Kimura Y,Suga H,Ueda K,Kato H

    更新日期:2014-03-18 00:00:00

  • Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex.

    abstract::Here, using further optimized 3D culture that allows highly selective induction and long-term growth of human ES cell (hESC)-derived cortical neuroepithelium, we demonstrate unique aspects of self-organization in human neocorticogenesis. Self-organized cortical tissue spontaneously forms a polarity along the dorsocaud...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1315710110

    authors: Kadoshima T,Sakaguchi H,Nakano T,Soen M,Ando S,Eiraku M,Sasai Y

    更新日期:2013-12-10 00:00:00

  • Drought mediates the importance of stochastic community assembly.

    abstract::Historically, the biodiversity and composition of species in a locality was thought to be influenced primarily by deterministic factors. In such cases, species' niches create differential responses to environmental conditions and interspecific interactions, which combine to determine that locality's biodiversity and s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0704350104

    authors: Chase JM

    更新日期:2007-10-30 00:00:00

  • Fidelity of replication of phage phi X174 DNA by DNA polymerase III holoenzyme: spontaneous mutation by misincorporation.

    abstract::DNA from phi X174 is replicated in vitro with a fidelity similar to that found genetically. A mutation of TAG leads to TGG may be induced, however, by varying the concentrations of deoxynucleoside triphosphates, with a frequency proportional to [dGTP]2/[dATP]. This complex concentration dependence is consistent with t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.10.4946

    authors: Fersht AR

    更新日期:1979-10-01 00:00:00

  • Prediction of intracellular exposure bridges the gap between target- and cell-based drug discovery.

    abstract::Inadequate target exposure is a major cause of high attrition in drug discovery. Here, we show that a label-free method for quantifying the intracellular bioavailability (Fic) of drug molecules predicts drug access to intracellular targets and hence, pharmacological effect. We determined Fic in multiple cellular assay...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1701848114

    authors: Mateus A,Gordon LJ,Wayne GJ,Almqvist H,Axelsson H,Seashore-Ludlow B,Treyer A,Matsson P,Lundbäck T,West A,Hann MM,Artursson P

    更新日期:2017-07-25 00:00:00

  • Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites.

    abstract::Protein phosphorylation plays a key role in vasopressin signaling in the renal-collecting duct. Large-scale identification and quantification of phosphorylation events triggered by vasopressin is desirable to gain a comprehensive systems-level understanding of this process. We carried out phosphoproteomic analysis of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0600895103

    authors: Hoffert JD,Pisitkun T,Wang G,Shen RF,Knepper MA

    更新日期:2006-05-02 00:00:00

  • Oxygen-collagen priority and the early metazoan fossil record.

    abstract::The thesis is developed that a low oxygen level Precambrian atmosphere presented early-evolving metazoan organisms with physiological connective tissue priorities resulting from the important molecular oxygen requirements in the biosynthesis of collagen hydroxyproline. Shells, cuticles, and carapaces which are not man...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.65.4.781

    authors: Towe KM

    更新日期:1970-04-01 00:00:00

  • Asymmetry in corticofugal modulation of frequency-tuning in mustached bat auditory system.

    abstract::Focal electric stimulation of the auditory cortex is well suited for exploration of the function of the corticofugal (descending) system and the neural mechanism of plasticity in the central auditory system, because it evokes changes in frequency-tuning, called best frequency (BF) shifts, as does auditory fear conditi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0509761102

    authors: Xiao Z,Suga N

    更新日期:2005-12-27 00:00:00

  • Human cytomegalovirus latent infection of granulocyte-macrophage progenitors.

    abstract::We have investigated the interaction of human cytomegalovirus (CMV) with cultured primary granulocyte-macrophage progenitors, a suspected natural site of viral latency, and have established conditions for latent infection and reactivation in this cell population. Progenitor cells from human fetal liver or bone marrow ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.25.11879

    authors: Kondo K,Kaneshima H,Mocarski ES

    更新日期:1994-12-06 00:00:00

  • 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors up-regulate transforming growth factor-beta signaling in cultured heart cells via inhibition of geranylgeranylation of RhoA GTPase.

    abstract::Transforming growth factor-beta (TGFbeta) signaling has been shown to play a role in cardiac development as well as in the pathogenesis of cardiovascular disease. Prior studies have suggested a relationship between cholesterol metabolism and TGFbeta signaling. Here we demonstrate that induction of the cholesterol meta...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.20.11525

    authors: Park HJ,Galper JB

    更新日期:1999-09-28 00:00:00

  • Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for α-1-antitrypsin deficiency.

    abstract::Adeno-associated virus (AAV)-mediated gene therapy is currently being pursued as a treatment for the monogenic disorder α-1-antitrypsin (AAT) deficiency. Results from phase I and II studies have shown relatively stable and dose-dependent increases in transgene-derived wild-type AAT after local intramuscular vector adm...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,多中心研究

    doi:10.1073/pnas.1617726114

    authors: Calcedo R,Somanathan S,Qin Q,Betts MR,Rech AJ,Vonderheide RH,Mueller C,Flotte TR,Wilson JM

    更新日期:2017-02-14 00:00:00

  • Identification, sequence, and expression of caveolin-2 defines a caveolin gene family.

    abstract::Caveolin, a 21- to 24-kDa integral membrane protein, is a principal component of caveolae membranes. Caveolin interacts directly with heterotrimeric guanine nucleotide binding proteins (G proteins) and can functionally regulate their activity. Here, an approximately 20-kDa caveolin-related protein, caveolin-2, was ide...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.1.131

    authors: Scherer PE,Okamoto T,Chun M,Nishimoto I,Lodish HF,Lisanti MP

    更新日期:1996-01-09 00:00:00

  • Homology and functional similarity of an hrp-linked pathogenicity locus, dspEF, of Erwinia amylovora and the avirulence locus avrE of Pseudomonas syringae pathovar tomato.

    abstract::The "disease-specific" (dsp) region next to the hrp gene cluster of Erwinia amylovora is required for pathogenicity but not for elicitation of the hypersensitive reaction. A 6.6-kb apparent operon, dspEF, was found responsible for this phenotype. The operon contains genes dspE and dspF and is positively regulated by h...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.3.1325

    authors: Bogdanove AJ,Kim JF,Wei Z,Kolchinsky P,Charkowski AO,Conlin AK,Collmer A,Beer SV

    更新日期:1998-02-03 00:00:00

  • Conformational plasticity of glycogenin and its maltosaccharide substrate during glycogen biogenesis.

    abstract::Glycogenin initiates the synthesis of a maltosaccharide chain covalently attached to itself on Tyr195 via a stepwise glucosylation reaction, priming glycogen synthesis. We have captured crystallographic snapshots of human glycogenin during its reaction cycle, revealing a dynamic conformational switch between ground an...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1113921108

    authors: Chaikuad A,Froese DS,Berridge G,von Delft F,Oppermann U,Yue WW

    更新日期:2011-12-27 00:00:00

  • Chromatin-interaction compartment switch at developmentally regulated chromosomal domains reveals an unusual principle of chromatin folding.

    abstract::Several 400- to 800-kb murine chromosome domains switch from early to late replication during loss of pluripotency, accompanied by a stable form of gene silencing that is resistant to reprogramming. We found that, whereas enhanced nuclease accessibility correlated with early replication genome-wide, domains that switc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1207185109

    authors: Takebayashi S,Dileep V,Ryba T,Dennis JH,Gilbert DM

    更新日期:2012-07-31 00:00:00

  • A transmissible plasmid controlling camphor oxidation in Pseudomonas putida.

    abstract::Earlier papers demonstrated an extensive genetic exchange among fluorescent Pseudomonads; this one documents for genes specifying enzymes of peripheral dissimilation an extrachromosomal array, segregation, and frequent interstrain transfer. An hypothesis is presented of a general mechanism for the formation and mainte...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.70.3.885

    authors: Rheinwald JG,Chakrabarty AM,Gunsalus IC

    更新日期:1973-03-01 00:00:00

  • A CACGTG motif of the Antirrhinum majus chalcone synthase promoter is recognized by an evolutionarily conserved nuclear protein.

    abstract::In the chalcone synthase gene of Antirrhinum majus (snapdragon), 150 base pairs of the 5' flanking region contain cis-acting signals for UV light-induced expression. A nuclear factor, designated CG-1, specifically recognizes a hexameric motif with internal dyad symmetry, CACGTG, located within this light-responsive se...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.18.6930

    authors: Staiger D,Kaulen H,Schell J

    更新日期:1989-09-01 00:00:00

  • A Drosophila orphan G protein-coupled receptor BOSS functions as a glucose-responding receptor: loss of boss causes abnormal energy metabolism.

    abstract::Glucose, one of the most important nutrients for animals, acts as a regulatory signal that controls the secretion of hormones, such as insulin, by endocrine tissues. However, how organisms respond to extracellular glucose and how glucose controls nutrient homeostasis remain unknown. Here, we show that a putative Droso...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0807833105

    authors: Kohyama-Koganeya A,Kim YJ,Miura M,Hirabayashi Y

    更新日期:2008-10-07 00:00:00

  • Reciprocity or near-reciprocity of highly coupled enzymatic processes at the multidimensional inflection point.

    abstract::It has recently been demonstrated that coupled enzymatic processes may possess, for a particular choice of the state variables, multidimensional inflection points in thermodynamic force-flow space. The conditions for reciprocity in the linear region near such a reference state, which may be far from equilibrium, are o...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.7.4314

    authors: Caplan SR

    更新日期:1981-07-01 00:00:00

  • Linker insertion mutagenesis of the human immunodeficiency virus reverse transcriptase expressed in bacteria: definition of the minimal polymerase domain.

    abstract::A plasmid construct expressing the p66 version of the human immunodeficiency virus reverse transcriptase as a bacterial fusion protein was subjected to in vitro mutagenesis, and the resulting variant proteins were assayed to define the locations of the two major enzymatic activities. The DNA polymerase activity was lo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.9.3104

    authors: Prasad VR,Goff SP

    更新日期:1989-05-01 00:00:00

  • Proteins from eight eukaryotic cytochrome P-450 families share a segmented region of sequence similarity.

    abstract::Proteins from eight eukaryotic families in the cytochrome P-450 superfamily share one region of sequence similarity. This region begins 275-310 amino acids from the amino terminus of each P-450, continues for approximately 170 residues, and ends 35-50 amino acids before the carboxyl terminus. The region can be divided...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.19.7221

    authors: Kalb VF,Loper JC

    更新日期:1988-10-01 00:00:00

  • Membrane-bound MinDE complex acts as a toggle switch that drives Min oscillation coupled to cytoplasmic depletion of MinD.

    abstract::The Escherichia coli Min system self-organizes into a cell-pole to cell-pole oscillator on the membrane to prevent divisions at the cell poles. Reconstituting the Min system on a lipid bilayer has contributed to elucidating the oscillatory mechanism. However, previous in vitro patterns were attained with protein densi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1600644113

    authors: Vecchiarelli AG,Li M,Mizuuchi M,Hwang LC,Seol Y,Neuman KC,Mizuuchi K

    更新日期:2016-03-15 00:00:00

  • Further comments on the ascorbic acid requirement.

    abstract::Recommended Daily Allowances (US RDA) of the Food and Drug Administration for ascorbic acid are higher than Recommended Dietary Allowances (set by the Food and Nutrition Board) for adults. There is a 6-fold margin between the requirement to prevent scurvy and the US RDA. The high requirement reported for the rhesus mo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.10.4151

    authors: Jukes TH

    更新日期:1975-10-01 00:00:00

  • Combinatorial interactions of serpent, lozenge, and U-shaped regulate crystal cell lineage commitment during Drosophila hematopoiesis.

    abstract::The GATA factor Serpent (Srp) is required for hemocyte precursor formation during Drosophila hematopoiesis. These blood cell progenitors give rise to two distinct lineages within the developing embryo. Lozenge, a Runx protein homologue, and Glial cells missing-1 and -2 are essential for crystal cell and plasmatocyte p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1635050100

    authors: Fossett N,Hyman K,Gajewski K,Orkin SH,Schulz RA

    更新日期:2003-09-30 00:00:00

  • Large-scale mechanical properties of Xenopus embryonic epithelium.

    abstract::Epithelia are planar tissues that undergo major morphogenetic movements during development. These movements must work in the context of the mechanical properties of epithelia. Surprisingly little is known about these mechanical properties at the time and length scales of morphogenetic processes. We show that at a time...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1010331108

    authors: Luu O,David R,Ninomiya H,Winklbauer R

    更新日期:2011-03-08 00:00:00

  • Bombyx prothoracicostatic peptides activate the sex peptide receptor to regulate ecdysteroid biosynthesis.

    abstract::Insect molting and metamorphosis are induced by steroid hormones named ecdysteroids, whose production is regulated by various neuropeptides. We cloned the gene and analyzed the expression of the prothoracicostatic peptide, a unique neuropeptide shown to suppress the production of ecdysteroids in the prothoracic gland ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0907471107

    authors: Yamanaka N,Hua YJ,Roller L,Spalovská-Valachová I,Mizoguchi A,Kataoka H,Tanaka Y

    更新日期:2010-02-02 00:00:00

  • Specific release of the thioesterase component of the fatty acid synthetase multienzyme complex by limited trypsinization.

    abstract::Limited trypsinization of the fatty acid synthetase multienzyme complex from rat mammary gland results in the release of a protein, molecular weight 32,000, with thioesterase activity. The other components of the multienzyme complex--the acyl carrier protein, acetyl and malonyl transferases, condensing enzyme, keto re...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.73.4.1184

    authors: Smith S,Agradi E,Libertini L,Dileepan KN

    更新日期:1976-04-01 00:00:00

  • Variability of signal sequences in turn-taking exchanges induces agency attribution in 10.5-mo-olds.

    abstract::Infants' sensitivity to contingent reactivity as an indicator of intentional agency has been demonstrated by numerous referential gaze-following studies. Here we propose that variability of signal sequences in a turn-taking exchange provides an informative cue for infants to recognize interactions that may involve com...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1816709116

    authors: Tauzin T,Gergely G

    更新日期:2019-07-30 00:00:00