Function and regulation of class I ribonucleotide reductase-encoding genes in mycobacteria.

Abstract:

:Ribonucleotide reductases (RNRs) are crucial to all living cells, since they provide deoxyribonucleotides (dNTPs) for DNA synthesis and repair. In Mycobacterium tuberculosis, a class Ib RNR comprising nrdE- and nrdF2-encoded subunits is essential for growth in vitro. Interestingly, the genome of this obligate human pathogen also contains the nrdF1 (Rv1981c) and nrdB (Rv0233) genes, encoding an alternate class Ib RNR small (R2) subunit and a putative class Ic RNR R2 subunit, respectively. However, the role(s) of these subunits in dNTP provision during M. tuberculosis pathogenesis is unknown. In this study, we demonstrate that nrdF1 and nrdB are dispensable for the growth and survival of M. tuberculosis after exposure to various stresses in vitro and, further, that neither gene is required for growth and survival in mice. These observations argue against a specialist role for the alternate R2 subunits under the conditions tested. Through the construction of nrdR-deficient mutants of M. tuberculosis and Mycobacterium smegmatis, we establish that the genes encoding the essential class Ib RNR subunits are specifically regulated by an NrdR-type repressor. Moreover, a strain of M. smegmatis mc(2)155 lacking the 56-kb chromosomal region, which includes duplicates of nrdHIE and nrdF2, and a mutant retaining only one copy of nrdF2 are shown to be hypersensitive to the class I RNR inhibitor hydroxyurea as a result of depleted levels of the target. Together, our observations identify a potential vulnerability in dNTP provision in mycobacteria and thereby offer a compelling rationale for pursuing the class Ib RNR as a target for drug discovery.

journal_name

J Bacteriol

journal_title

Journal of bacteriology

authors

Mowa MB,Warner DF,Kaplan G,Kana BD,Mizrahi V

doi

10.1128/JB.01409-08

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

985-95

issue

3

eissn

0021-9193

issn

1098-5530

pii

JB.01409-08

journal_volume

191

pub_type

杂志文章
  • Transient Intestinal Colonization by a Live-Attenuated Oral Cholera Vaccine Induces Protective Immune Responses in Streptomycin-Treated Mice.

    abstract::Current mouse models for evaluating the efficacy of live oral cholera vaccines (OCVs) have important limitations. Conventionally raised adult mice are resistant to intestinal colonization by Vibrio cholerae, but germfree mice can be colonized and have been used to study OCV immunogenicity. However, germfree animals ha...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.00232-20

    authors: Fakoya B,Sit B,Waldor MK

    更新日期:2020-11-19 00:00:00

  • Asparaginase II of Saccharomyces cerevisiae: selection of four mutations that cause derepressed enzyme synthesis.

    abstract::A positive selection method was used to isolate four Saccharomyces cerevisiae mutations that cause derepressed synthesis of asparaginase II. The four mutations (and1, and2, and3, and4) were neither closely linked to each other nor linked to previously characterized mutations (asp3, asp6) which cause the complete loss ...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.165.1.293-296.1986

    authors: Kamerud JQ,Roon RJ

    更新日期:1986-01-01 00:00:00

  • Cyclic diguanylic acid and cellulose synthesis in Agrobacterium tumefaciens.

    abstract::The occurrence of the novel regulatory nucleotide bis(3',5')-cyclic diguanylic acid (c-di-GMP) and its relation to cellulose biogenesis in the plant pathogen Agrobacterium tumefaciens was studied. c-di-GMP was detected in acid extracts of 32P-labeled cells grown in various media, and an enzyme responsible for its form...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.171.12.6649-6655.1989

    authors: Amikam D,Benziman M

    更新日期:1989-12-01 00:00:00

  • IDENTIFICATION OF THE STRUCTURAL GENE FOR BETA-GLUCOSIDASE IN SACCHAROMYCES LACTIS.

    abstract::Herman, Alberta (University of Wisconsin, Madison) and Harlyn Halvorson. Identification of the structural gene for beta-glucosidase in Saccharomyces lactis. J. Bacteriol. 85:895-900. 1963.-Three allelic forms (B(h, m, l)) of the structural gene for beta-glucosidase have been identified in the yeast Saccharomyces lacti...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.85.4.895-900.1963

    authors: HERMAN A,HALVORSON H

    更新日期:1963-04-01 00:00:00

  • Carrier-mediated transport of folate in a mutant of Pediococcus cerevisiae.

    abstract::A mutant strain of Pediococcus cerevisiae (P. cerevisiae/PteGlu) was isolated which grows on low-folate (PteGlu) concentrations (200 pg/ml). The growth response of the parent and mutant strains to folinate (5-CHO-H(4)PteGlu) was the same. The transport of (14)C-PteGlu by P. cerevisiae/PteGlu was temperature-dependent ...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.114.2.485-490.1973

    authors: Mandelbaum-Shavit F,Grossowicz N

    更新日期:1973-05-01 00:00:00

  • Structure and composition of the cell wall of Neurospora crassa.

    abstract::The structure and composition of the cell walls of hyphae of Neurospora crassa were investigated by electron microscopy, chemical analysis, and X-ray diffraction both before and after progressive enzymatic degradation by snail gut enzymes, chitinase, and trypsin. The wall consists of two phases: randomly disposed skel...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.94.1.202-212.1967

    authors: Manocha MS,Colvin JR

    更新日期:1967-07-01 00:00:00

  • Purification and characterization of fimbriae from Salmonella enteritidis.

    abstract::A human isolate of Salmonella enteritidis which displayed strong pellicle formation during static broth culture and mannose-sensitive hemagglutination produced fimbriae which were morphologically indistinguishable from type 1 fimbriae of members of the family Enterobacteriaceae. Fimbrin was purified to homogeneity, an...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.168.1.221-227.1986

    authors: Feutrier J,Kay WW,Trust TJ

    更新日期:1986-10-01 00:00:00

  • Propanediol utilization genes (pdu) of Salmonella typhimurium: three genes for the propanediol dehydratase.

    abstract::The propanediol utilization (pdu) operon of Salmonella typhimurium encodes proteins required for the catabolism of propanediol, including a coenzyme B12-dependent propanediol dehydratase. A clone that expresses propanediol dehydratase activity was isolated from a Salmonella genomic library. DNA sequence analysis showe...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.179.21.6633-6639.1997

    authors: Bobik TA,Xu Y,Jeter RM,Otto KE,Roth JR

    更新日期:1997-11-01 00:00:00

  • Mutational analysis of the signal-sensing domain of ResE histidine kinase from Bacillus subtilis.

    abstract::The Bacillus subtilis ResD-ResE two-component regulatory system activates genes involved in nitrate respiration in response to oxygen limitation or nitric oxide (NO). The sensor kinase ResE activates the response regulator ResD through phosphorylation, which then binds to the regulatory region of genes involved in ana...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.186.6.1694-1704.2004

    authors: Baruah A,Lindsey B,Zhu Y,Nakano MM

    更新日期:2004-03-01 00:00:00

  • Physiological analysis of the stringent response elicited in an extreme thermophilic bacterium, Thermus thermophilus.

    abstract::Guanosine tetraphosphate (ppGpp) is a key mediator of stringent control, an adaptive response of bacteria to amino acid starvation, and has thus been termed a bacterial alarmone. Previous X-ray crystallographic analysis has provided a structural basis for the transcriptional regulation of RNA polymerase activity by pp...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.00574-06

    authors: Kasai K,Nishizawa T,Takahashi K,Hosaka T,Aoki H,Ochi K

    更新日期:2006-10-01 00:00:00

  • Novel class of mutations of pilS mutants, encoding plasmid R64 type IV prepilin: interface of PilS-PilV interactions.

    abstract::The type IV pili of plasmid R64 belonging to the type IVB group are required only for liquid mating. They consist of the major and minor components PilS pilin and PilV adhesin, respectively. PilS pilin is first synthesized as a 22-kDa prepilin from the pilS gene and is then processed to a 19-kDa mature pilin by PilU p...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.01204-07

    authors: Shimoda E,Muto T,Horiuchi T,Furuya N,Komano T

    更新日期:2008-02-01 00:00:00

  • A chimeric N-terminal Escherichia coli--C-terminal Rhodobacter sphaeroides FliG rotor protein supports bidirectional E. coli flagellar rotation and chemotaxis.

    abstract::Flagellate bacteria such as Escherichia coli and Salmonella enterica serovar Typhimurium typically express 5 to 12 flagellar filaments over their cell surface that rotate in clockwise (CW) and counterclockwise directions. These bacteria modulate their swimming direction towards favorable environments by biasing the di...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.187.5.1695-1701.2005

    authors: Morehouse KA,Goodfellow IG,Sockett RE

    更新日期:2005-03-01 00:00:00

  • Glucomannan-mediated attachment of Rhizobium leguminosarum to pea root hairs is required for competitive nodule infection.

    abstract::The Rhizobium leguminosarum biovar viciae genome contains several genes predicted to determine surface polysaccharides. Mutants predicted to affect the initial steps of polysaccharide synthesis were identified and characterized. In addition to the known cellulose (cel) and acidic exopolysaccharide (EPS) (pss) genes, w...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.01694-07

    authors: Williams A,Wilkinson A,Krehenbrink M,Russo DM,Zorreguieta A,Downie JA

    更新日期:2008-07-01 00:00:00

  • Quantitation of the action of ethylenediaminetetracetic acid and tris(hydroxymethyl)aminomethane on a gram-negative bacterium by vancomycin adsorption.

    abstract::Changes in the cell wall of a species of Flavobacterium can be quantitated by measuring vancomycin adsorption. Treatment of the cells with ethylenediaminetetraacetic acid or tris(hydroxymethyl)aminomethane (or both) increased adsorption of the antibiotic. ...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.103.2.523-524.1970

    authors: Haslam DF,Best GK,Durham NN

    更新日期:1970-08-01 00:00:00

  • Nuclear deoxyribonucleic acid-dependent ribonucleic acid polymerases from Saccharomyces cerevisiae.

    abstract::Two deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerases (I, II) have been solubilized from isolated Saccharomyces cerevisiae nuclei. The enzymes can be separated by chromatography on O-diethylaminoethyl Sephadex. Both enzymes are active with high-molecular-weight nuclear yeast DNA, although RNA po...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.114.1.1-6.1973

    authors: Sebastian J,Bhargava MM,Halvorson HO

    更新日期:1973-04-01 00:00:00

  • Abnormal septation and inhibition of sporulation by accumulation of L- -glycerophosphate in Bacillus subtilis mutants.

    abstract::Accumulation of l-alpha-glycerophosphate, in cells of Bacillus subtilis mutants lacking the nicotinamide adenine dinucleotide-independent glycerophosphate dehydrogenase activity, suppresses both growth and sporulation. After growth has stopped, the cells slowly develop one and later more asymmetric septa that are thic...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.113.2.1034-1045.1973

    authors: O YK,Freese EB,Freese E

    更新日期:1973-02-01 00:00:00

  • The MscS and MscL families of mechanosensitive channels act as microbial emergency release valves.

    abstract::Single-celled organisms must survive exposure to environmental extremes. Perhaps one of the most variable and potentially life-threatening changes that can occur is that of a rapid and acute decrease in external osmolarity. This easily translates into several atmospheres of additional pressure that can build up within...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章,评审

    doi:10.1128/JB.00576-12

    authors: Booth IR,Blount P

    更新日期:2012-09-01 00:00:00

  • Identification of an operon involved in sulfolipid biosynthesis in Rhodobacter sphaeroides.

    abstract::Two new mutants of Rhodobacter sphaeroides deficient in sulfolipid accumulation were isolated by directly screening mutagenized cell lines for polar lipid composition by thin-layer chromatography of lipid extracts. A genomic clone which complemented the mutations in these two lines, but not the previously described su...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.174.20.6479-6487.1992

    authors: Benning C,Somerville CR

    更新日期:1992-10-01 00:00:00

  • Mating pheromones of Saccharomyces kluyveri: pheromone interactions between Saccharomyces kluyveri and Saccharomyces cerevisiae.

    abstract::Saccharomyces kluyveri is a heterothallic yeast with two allelic mating types denoted as a-k and alpha-k by analogy with Saccharomyces cerevisiae and from the work described here. S. kluyveri produces mating pheromones analogous to those of S. cerevisiae, but which appear to have different specificity. S. kluyveri thu...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.138.1.146-154.1979

    authors: McCullough J,Herskowitz I

    更新日期:1979-04-01 00:00:00

  • The tdh and serA operons of Escherichia coli: mutational analysis of the regulatory elements of leucine-responsive genes.

    abstract::The tdh promoter of Escherichia coli is induced seven- to eightfold when cells are grown in the presence of exogenous leucine. A scheme was devised to select mutants that exhibited high constitutive expression of the tdh promoter. The mutations in these strains were shown to lie within a previously identified gene (lr...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.173.19.5944-5953.1991

    authors: Rex JH,Aronson BD,Somerville RL

    更新日期:1991-10-01 00:00:00

  • Inoculum-dependent division lag of Bacillus cultures and its relation to an endogenous factor(s) ("schizokinen").

    abstract::Lankford, C. E. (The University of Texas, Austin), James R. Walker, James B. Reeves, N. H. Nabbut, B. R. Byers, and R. J. Jones. Inoculum-dependent division lag of Bacillus cultures and its relation to an endogenous factor(s) ("schizokinen"). J. Bacteriol. 91:1070-1079. 1966.-When cells of Bacillus megaterium, grown o...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.91.3.1070-1079.1966

    authors: Lankford CE,Walker JR,Reeves JB,Nabbut NH,Byers BR,Jones RJ

    更新日期:1966-03-01 00:00:00

  • Degradation of pyruvate by Micrococcus lactilyticus. III. Properties and cofactor requirements of the carbon dioxide-exchange reaction.

    abstract::Whiteley, H. R. (University of Washington, Seattle) and N. G. McCormick. Degradation of pyruvate by Micrococcus lactilyticus. III. Properties and cofactor requirements of the carbon dioxide-exchange reaction. J. Bacteriol. 85:382-393. 1963.-At an acid pH, extracts of Micrococcus lactilyticus (Veillonella alcalescens) ...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.85.2.382-393.1963

    authors: WHITELEY HR,McCORMICK NG

    更新日期:1963-02-01 00:00:00

  • A family of insertion sequences that impacts integrons by specific targeting of gene cassette recombination sites, the IS1111-attC Group.

    abstract::Integrons facilitate the evolution of complex phenotypes by physical and transcriptional linkage of genes. They can be categorized as chromosomal integrons (CIs) or mobile resistance integrons (MRIs). The significance of MRIs for the problem of multiple antibiotic resistance is well established. CIs are more widesprea...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.00229-08

    authors: Tetu SG,Holmes AJ

    更新日期:2008-07-01 00:00:00

  • Molecular analysis of the cryptic and functional phn operons for phosphonate use in Escherichia coli K-12.

    abstract::We cloned the cryptic phn operon of a K-12 strain, phn(EcoK), and analyzed the nucleotide sequence of the phn region (11,672 bp). An mRNA start site upstream of the phnC gene was identified by S1 nuclease mapping. The pho regulon activator PhoB protects a pho box region near the mRNA start in DNase I footprinting and ...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.173.8.2665-2672.1991

    authors: Makino K,Kim SK,Shinagawa H,Amemura M,Nakata A

    更新日期:1991-04-01 00:00:00

  • Phototaxis and membrane potential in the photosynthetic bacterium Rhodospirillum rubrum.

    abstract::Cells of the photosynthetic bacterium Rhodospirillum rubrum cultivated anaerobically in light show phototaxis. The behavior of individual cells in response to the phenomenon is reversal(s) of the swimming direction when the intensity of the light available to them abruptly decreases. The tactic response was inhibited ...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.131.1.34-41.1977

    authors: Harayama S,Iino T

    更新日期:1977-07-01 00:00:00

  • Plasmid-to-chromosome gene transfer in Haemophilus influenza during growth.

    abstract::A low level of recombination between homologous regions of plasmids and the host chromosome occurred during cell growth. The plasmids contained antibiotic resistance markers on the homologous regions which were only expressed when they were integrated into the chromosome. Such recombination took place in Rec+ rec-2 mu...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.168.1.458-459.1986

    authors: Balganesh M,Arrigoni L,Setlow JK

    更新日期:1986-10-01 00:00:00

  • Structure and Membrane Topography of the Vibrio-Type Secretin Complex from the Type 2 Secretion System of Enteropathogenic Escherichia coli.

    abstract::The β-barrel assembly machinery (BAM) complex is the core machinery for the assembly of β-barrel membrane proteins, and inhibition of BAM complex activity is lethal to bacteria. Discovery of integral membrane proteins that are key to pathogenesis and yet do not require assistance from the BAM complex raises the questi...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.00521-17

    authors: Hay ID,Belousoff MJ,Dunstan RA,Bamert RS,Lithgow T

    更新日期:2018-02-07 00:00:00

  • Lactate dehydrogenase activity in certain strains of Staphylococcus aureus.

    abstract::Lactate dehydrogenase (LDH) was studied in phage-propagating strains 29, 3A, 6, 81, and 42D of Staphylococcus aureus selected from the five groups in the International-Blair series. Cells were cultivated in Brain Heart Infusion (Difco) under nearly anaerobic conditions and were harvested near the end of the log phase....

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.95.1.74-80.1968

    authors: Stockland AE,San Clemente CL

    更新日期:1968-01-01 00:00:00

  • Conservation of structure and location of Rhizobium meliloti and Klebsiella pneumoniae nifB genes.

    abstract::Using transposon Tn5-mediated mutagenesis, an essential Rhizobium meliloti nitrogen fixation (nif) gene was identified and located directly downstream of the regulatory gene nifA. Maxicell and DNA sequence analysis demonstrated that the new gene is transcribed in the same direction as nifA and codes for a 54-kilodalto...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/jb.169.3.1120-1126.1987

    authors: Buikema WJ,Klingensmith JA,Gibbons SL,Ausubel FM

    更新日期:1987-03-01 00:00:00

  • ROLE OF MARINE FUNGI IN THE BIOCHEMISTRY OF THE OCEANS. IV. GROWTH RESPONSES TO SEAWATER INORGANIC MACROCONSTITUENTS.

    abstract::Sguros, Peter L. (University of Miami, Miami, Fla.), and Jacqueline Simms. Role of marine fungi in the biochemistry of the oceans. IV. Growth responses to seawater inorganic macroconstituents. J. Bacteriol. 88:346-355. 1964.-The filamentous ascomycete Halosphaeria mediosetigera and the deuteromycete Culcitalna achrasp...

    journal_title:Journal of bacteriology

    pub_type: 杂志文章

    doi:10.1128/JB.88.2.346-355.1964

    authors: SGUROS PL,SIMMS J

    更新日期:1964-08-01 00:00:00