Site-directed mutagenesis of the katG gene of Mycobacterium tuberculosis: effects on catalase-peroxidase activities and isoniazid resistance.

Abstract:

:Recent studies examining the molecular mechanisms of isoniazid (INH) resistance in Mycobacterium tuberculosis have demonstrated that a significant percentage of drug-resistant strains are mutated in the katG gene which encodes a catalase-peroxidase, and the majority of these alterations are missense mutations which result in the substitution of a single amino acid. In previous reports, residues which may be critical for enzymatic activity and the drug-resistant phenotype have been identified by evaluating INH-resistant clinical isolates and in vitro mutants. In this study, site-directed mutagenesis techniques were utilized to alter the wild-type katG gene from M. tuberculosis at 13 of these codons. The effects of these mutations were determined using complementation assays in katG-defective, INH-resistant strains of Mycobacterium smegmatis and Mycobacterium bovis BCG. This mutational analysis revealed that point mutations in the katG gene at nine of the 13 codons can cause drug resistance, and that enzymatic activity and resistance to INH are inversely related. In addition, mutations in the mycobacterial catalase-peroxidase which reduce catalase activity also decrease peroxidase activity.

journal_name

Mol Microbiol

journal_title

Molecular microbiology

authors

Rouse DA,DeVito JA,Li Z,Byer H,Morris SL

doi

10.1046/j.1365-2958.1996.00133.x

subject

Has Abstract

pub_date

1996-11-01 00:00:00

pages

583-92

issue

3

eissn

0950-382X

issn

1365-2958

journal_volume

22

pub_type

杂志文章
  • Topology-dependent transcription in linear and circular plasmids of the segmented genome of Borrelia burgdorferi.

    abstract::The segmented genome of Borrelia burgdorferi, a causative agent of Lyme disease, contains a mixture of over 20 linear and circular plasmids. Genes encoding five paralogous families of plasmid replication proteins are located on both circular and linear DNA molecules. The effect of DNA topology on the transcription of ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2006.05533.x

    authors: Beaurepaire C,Chaconas G

    更新日期:2007-01-01 00:00:00

  • Novel coordination of lipopolysaccharide modifications in Vibrio cholerae promotes CAMP resistance.

    abstract::In the environment and during infection, the human intestinal pathogen Vibrio cholerae must overcome noxious compounds that damage the bacterial outer membrane. The El Tor and classical biotypes of O1 V. cholerae show striking differences in their resistance to membrane disrupting cationic antimicrobial peptides (CAMP...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13835

    authors: Herrera CM,Henderson JC,Crofts AA,Trent MS

    更新日期:2017-11-01 00:00:00

  • Alternate promoters direct stress-induced transcription of the Bacillus subtilis clpC operon.

    abstract::clpC of Bacillus subtilis is part of an operon containing six genes. Northern blot analysis suggested that all genes are co-transcribed and encode stress-inducible proteins. Two promoters (PA and PB) were mapped upstream of the first gene. PA resembles promoters recognized by the vegetative RNA polymerase E sigma A. T...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1996.tb02511.x

    authors: Krüger E,Msadek T,Hecker M

    更新日期:1996-05-01 00:00:00

  • The universal stress protein paralogues of Escherichia coli are co-ordinately regulated and co-operate in the defence against DNA damage.

    abstract::We have cloned, characterized and inactivated genes encoding putative UspA paralogues in Escherichia coli. The yecG (uspC), yiiT (uspD) and ydaA (uspE) genes were demonstrated to encode protein pro-ducts and these were mapped to spots in the E. coli proteomic database. Expression analysis using chromosomal transcripti...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2002.02720.x

    authors: Gustavsson N,Diez A,Nyström T

    更新日期:2002-01-01 00:00:00

  • PerC and GrlA independently regulate Ler expression in enteropathogenic Escherichia coli.

    abstract::Ler, encoded by the locus of enterocyte effacement (LEE) of attaching and effacing (A/E) pathogens, induces the expression of LEE genes by counteracting the silencing exerted by H-NS. Ler expression is modulated by several global regulators, and is activated by GrlA, which is also LEE-encoded. Typical enteropathogenic...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2011.07819.x

    authors: Bustamante VH,Villalba MI,García-Angulo VA,Vázquez A,Martínez LC,Jiménez R,Puente JL

    更新日期:2011-10-01 00:00:00

  • Analysis of the gene cluster involved in production and immunity of the peptide antibiotic AS-48 in Enterococcus faecalis.

    abstract::A region of 7.8 kb of the plasmid pMB2 from Enterococcus faecalis S-48 carrying the information necessary for production and immunity of the peptide antibiotic AS-48 has been cloned and sequenced. It contains the as-48A structural gene plus five open reading frames (as-48B, as-48C, as-48C1, as-48D and as-48D1). Beside...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1998.00682.x

    authors: Martínez-Bueno M,Valdivia E,Gálvez A,Coyette J,Maqueda M

    更新日期:1998-01-01 00:00:00

  • N-mediated transcription antitermination in lambdoid phage H-19B is characterized by alternative NUT RNA structures and a reduced requirement for host factors.

    abstract::Gene expression in lambdoid phages in part is controlled by transcription antitermination. For most lambdoid phages, maximal expression of delayed early genes requires an RNA polymerase modified by the phage N and host Nus proteins at RNA NUT sites. The NUT sites (NUTL and NUTR) are made up of three elements: BOXA, BO...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2000.02217.x

    authors: Neely MN,Friedman DI

    更新日期:2000-12-01 00:00:00

  • The DivJ, CbrA and PleC system controls DivK phosphorylation and symbiosis in Sinorhizobium meliloti.

    abstract::Sinorhizobium meliloti is a soil bacterium that invades the root nodules it induces on Medicago sativa, whereupon it undergoes an alteration of its cell cycle and differentiates into nitrogen-fixing, elongated and polyploid bacteroid with higher membrane permeability. In Caulobacter crescentus, a related alphaproteoba...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12347

    authors: Pini F,Frage B,Ferri L,De Nisco NJ,Mohapatra SS,Taddei L,Fioravanti A,Dewitte F,Galardini M,Brilli M,Villeret V,Bazzicalupo M,Mengoni A,Walker GC,Becker A,Biondi EG

    更新日期:2013-10-01 00:00:00

  • Relaxosome function and conjugation regulation in F-like plasmids - a structural biology perspective.

    abstract::The tra operon of the prototypical F plasmid and its relatives enables transfer of a copy of the plasmid to other bacterial cells via the process of conjugation. Tra proteins assemble to form the transferosome, the transmembrane pore through which the DNA is transferred, and the relaxosome, a complex of DNA-binding pr...

    journal_title:Molecular microbiology

    pub_type: 杂志文章,评审

    doi:10.1111/j.1365-2958.2012.08131.x

    authors: Wong JJ,Lu J,Glover JN

    更新日期:2012-08-01 00:00:00

  • Characterization of RAT, an autolysis regulator in Staphylococcus aureus.

    abstract::In trying to identify genetic loci involved in the regulation of cap5 genes in Staphylococcus aureus, we isolated a transposon mutant that exhibited a growth defect, enhanced autolysis and increased sensitivity to Triton X-100 and penicillin, attributable in part to increased murein hydrolase activity. Analysis of the...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2003.03503.x

    authors: Ingavale SS,Van Wamel W,Cheung AL

    更新日期:2003-06-01 00:00:00

  • Roles of three FurA paralogs in the regulation of genes pertaining to peroxide defense in Mycobacterium smegmatis mc2 155.

    abstract::Mycobacterium smegmatis mc2 155 has three genes (MSMEG_6383, furA1; MSMEG_3460, furA2; MSMEG_6253, furA3) encoding FurA (ferric-uptake regulator A) paralogs. Three FurA paralogs in M. smegmatis are functionally redundant and negatively regulate expression of a subset of genes involved in peroxide detoxification such a...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.13956

    authors: Lee HN,Ji CJ,Lee HH,Park J,Seo YS,Lee JW,Oh JI

    更新日期:2018-06-01 00:00:00

  • Bacillus subtilis FolE is sustained by the ZagA zinc metallochaperone and the alarmone ZTP under conditions of zinc deficiency.

    abstract::Bacteria tightly regulate intracellular zinc levels to ensure sufficient zinc to support essential functions, while preventing toxicity. The bacterial response to zinc limitation includes the expression of putative zinc metallochaperones belonging to subfamily 1 of the COG0523 family of G3E GTPases. However, the clien...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.14314

    authors: Chandrangsu P,Huang X,Gaballa A,Helmann JD

    更新日期:2019-09-01 00:00:00

  • Regulation of Rfa2 phosphorylation in response to genotoxic stress in Candida albicans.

    abstract::Successful pathogens must be able to swiftly respond to and repair DNA damages inflicted by the host defence. The replication protein A (RPA) complex plays multiple roles in DNA damage response and is regulated by phosphorylation. However, the regulators of RPA phosphorylation remain unclear. Here, we investigated Rfa...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12749

    authors: Gao J,Wang H,Wong AH,Zeng G,Huang Z,Wang Y,Sang J,Wang Y

    更新日期:2014-10-01 00:00:00

  • Functional analysis of the Helicobacter pylori principal sigma subunit of RNA polymerase reveals that the spacer region is important for efficient transcription.

    abstract::We have cloned the rpoD gene encoding the principal sigma (sigma) factor of Helicobacter pylori. The deduced amino acid sequence reveals a predicted polypeptide of 676 residues that has amino acid homology with the principal sigma factors of a number of divergent prokaryotes. We have designated this factor sigma80. Am...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1998.01043.x

    authors: Beier D,Spohn G,Rappuoli R,Scarlato V

    更新日期:1998-10-01 00:00:00

  • Neisseria gonorrhoeae acquires mutations in analogous regions of gyrA and parC in fluoroquinolone-resistant isolates.

    abstract::Neisseria gonorrhoeae homologues of gyrA and parC have been identified using hybridization probes generated from conserved regions of diverse gyrA genes. These genes have been tentatively identified as gyrA and parC, based on predicted amino acid sequence homologies to known GyrA homologues from numerous bacterial spe...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb01297.x

    authors: Belland RJ,Morrison SG,Ison C,Huang WM

    更新日期:1994-10-01 00:00:00

  • Cloning and characterization of three genes (SUT1-3) encoding glucose transporters of the yeast Pichia stipitis.

    abstract::We have identified and characterized three genes, SUT1, SUT2 and SUT3, that encode glucose transporters of the yeast Pichia stipitis. When expressed in a Saccharomyces cerevisiae hxt null mutant strain that is unable to take up monosaccharides, all three proteins restored growth on glucose. Sequencing of the genes rev...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1999.01224.x

    authors: Weierstall T,Hollenberg CP,Boles E

    更新日期:1999-02-01 00:00:00

  • A gene involved in both protein secretion during growth and starvation-induced development encodes a subunit of the NADH:ubiquinone oxidoreductase in Myxococcus xanthus.

    abstract::The secretion of numerous proteins during vegetative growth of Myxococcus xanthus, and the multicellular development cycle induced upon starvation of these bacteria, are partially interrelated in so far as mutants impaired in extracellular protein production are unable to undergo development. We have cloned and sequen...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.1997.2901655.x

    authors: Laval-Favre K,Letouvet-Pawlak B,Friedrich T,Alexandre J,Guespin-Michel JF

    更新日期:1997-03-01 00:00:00

  • Coupling of Escherichia coli hns mRNA levels to DNA synthesis by autoregulation: implications for growth phase control.

    abstract::The H-NS protein of enteric bacteria is one of the major proteins of the bacterial nucleoid and seems to play an important role in nucleoid structure. Transcription of the hns gene encoding the H-NS protein appears to be negatively regulated by H-NS itself both in vitro and in vivo. We have examined the role of this m...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1995.mmi_18010101.x

    authors: Free A,Dorman CJ

    更新日期:1995-10-01 00:00:00

  • IpaB mediates macrophage apoptosis induced by Shigella flexneri.

    abstract::Shigella flexneri kills macrophages through apoptosis, involving the induction of host cell DNA fragmentation and characteristic morphological changes. Shigella can only cause damage if it escapes from the phagolysosome into the cytoplasm. The S. flexneri cytotoxic genes have been localized to the ipa operon of shigel...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb00341.x

    authors: Zychlinsky A,Kenny B,Ménard R,Prévost MC,Holland IB,Sansonetti PJ

    更新日期:1994-02-01 00:00:00

  • Molecular cloning, partial purification, and characterization of a haemin-binding lipoprotein from Haemophilus influenzae type b.

    abstract::A library of genomic DNA fragments from Haemophilus influenzae type b (Hib) DL42 was constructed in plasmid pBR322, transformed into Escherichia coli strain RR1, and screened for recombinant clones with haemin-binding activity by plating onto haemin-containing agar. Expression of haemin-binding activity by clones corr...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1991.tb02107.x

    authors: Hanson MS,Hansen EJ

    更新日期:1991-02-01 00:00:00

  • Slow growth of Mycobacterium tuberculosis at acidic pH is regulated by phoPR and host-associated carbon sources.

    abstract::During pathogenesis, Mycobacterium tuberculosis (Mtb) colonizes environments, such as the macrophage or necrotic granuloma, that are acidic and rich in cholesterol and fatty acids. The goal of this study was to examine how acidic pH and available carbon sources interact to regulate Mtb physiology. Here we report that ...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12688

    authors: Baker JJ,Johnson BK,Abramovitch RB

    更新日期:2014-10-01 00:00:00

  • Cdv-based cell division and cell cycle organization in the thaumarchaeon Nitrosopumilus maritimus.

    abstract::Cell division is mediated by different mechanisms in different evolutionary lineages. While bacteria and euryarchaea utilize an FtsZ-based mechanism, most crenarchaea divide using the Cdv system, related to the eukaryotic ESCRT-III machinery. Intriguingly, thaumarchaeal genomes encode both FtsZ and Cdv protein homolog...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2011.07834.x

    authors: Pelve EA,Lindås AC,Martens-Habbena W,de la Torre JR,Stahl DA,Bernander R

    更新日期:2011-11-01 00:00:00

  • Group A streptococcal growth phase-associated virulence factor regulation by a novel operon (Fas) with homologies to two-component-type regulators requires a small RNA molecule.

    abstract::A novel growth phase-associated two-component-type regulator, Fas (fibronectin/fibrinogen binding/haemolytic activity/streptokinase regulator), of Streptococcus pyogenes was identified in the M1 genome sequence, based on homologies to the histidine protein kinase (HPK) and response regulator (RR) part of the Staphyloc...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1046/j.1365-2958.2001.02226.x

    authors: Kreikemeyer B,Boyle MD,Buttaro BA,Heinemann M,Podbielski A

    更新日期:2001-01-01 00:00:00

  • Identification of a serine protease inhibitor which causes inclusion vacuole reduction and is lethal to Chlamydia trachomatis.

    abstract::The mechanistic details of the pathogenesis of Chlamydia, an obligate intracellular pathogen of global importance, have eluded scientists due to the scarcity of traditional molecular genetic tools to investigate this organism. Here we report a chemical biology strategy that has uncovered the first essential protease f...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/mmi.12306

    authors: Gloeckl S,Ong VA,Patel P,Tyndall JD,Timms P,Beagley KW,Allan JA,Armitage CW,Turnbull L,Whitchurch CB,Merdanovic M,Ehrmann M,Powers JC,Oleksyszyn J,Verdoes M,Bogyo M,Huston WM

    更新日期:2013-08-01 00:00:00

  • Characterization of a five-gene cluster required for the biogenesis of type 4 fimbriae in Pseudomonas aeruginosa.

    abstract::The opportunistic pathogen Pseudomonas aeruginosa produces type 4 fimbriae which promote adhesion to epithelial cells and are associated with a form of surface translocation called twitching motility. Transposon mutagenesis was used to identify loci required for fimbrial assembly or function by screening for mutants t...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1995.tb02414.x

    authors: Martin PR,Watson AA,McCaul TF,Mattick JS

    更新日期:1995-05-01 00:00:00

  • An acetylase with relaxed specificity catalyses protein N-terminal acetylation in Sulfolobus solfataricus.

    abstract::N-terminal protein acetylation is common in eukaryotes and halophilic archaea, but very rare in bacteria. We demonstrate that some of the most abundant proteins present in the crenarchaeote Sulfolobus solfataricus, including subunits of the thermosome, proteosome and ribosome, are acetylated at the N-terminus. Modific...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2007.05752.x

    authors: Mackay DT,Botting CH,Taylor GL,White MF

    更新日期:2007-06-01 00:00:00

  • Axiom of determining transcription start points by RNA polymerase in Escherichia coli.

    abstract::To investigate the determining factors in the selection of the transcription start points (tsp) by RNA polymerase of Escherichia coli, we systematically deleted or substituted single base pairs (bps) at 25 putative critical positions in the two extended -10 promoters, P1 and P2, of the gal operon. These changes extend...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.2004.04318.x

    authors: Lewis DE,Adhya S

    更新日期:2004-11-01 00:00:00

  • Cloning and characterization of fxp, the flexible pilin gene of Aeromonas hydrophila.

    abstract::The flexible pilus of Aeromonas hydrophila is a morphologically and biochemically unique organelle which binds eukaryotic cell surfaces and whose expression is induced by specific physiochemical conditions. fxp, the structural gene coding for the flexible pilus subunit, was localized on a 7.6kb plasmid of A. hydrophil...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1992.tb01449.x

    authors: Ho AS,Sohel I,Schoolnik GK

    更新日期:1992-09-01 00:00:00

  • The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation.

    abstract::Molecular analyses were applied to the genes encoding variants of the serosubtyping antigen, the class 1 outer membrane protein (PorA), from 55 serogroup A Neisseria meningitidis strains. These genes were evolutionarily stable and exhibited a limited range of genetic variation, primarily generated by recombination. Tr...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1994.tb01014.x

    authors: Suker J,Feavers IM,Achtman M,Morelli G,Wang JF,Maiden MC

    更新日期:1994-04-01 00:00:00

  • Sense and antisense transcripts of traM, a conjugal transfer gene of the antibiotic resistance plasmid R100.

    abstract::The region of the antibiotic resistance plasmid R100 that encodes the plasmid-specific transfer gene traM has two tandemly aligned promoters separated by 145 nucleotides. The principal transcripts are 705 and 562 nucleotides long. Minor transcripts are 1550 and 1700 nucleotides long. The 705-base transcript appears to...

    journal_title:Molecular microbiology

    pub_type: 杂志文章

    doi:10.1111/j.1365-2958.1989.tb00202.x

    authors: Dempsey WB

    更新日期:1989-04-01 00:00:00