Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus.: A 4.2-kb DNA fragment conferring quinolone res

The work described above continues our characterization of fluoroquinolone action against S. aureus (9, 19, 20,29, 39). In this organism, topoisomerase IV is the primary target of most fluoroquinolones (16, 17, 29), and so its sensitivity is a key aspect of drug action. As with gyrase, the physiological observations appear to derive from the formation of quinolone-topoisomerase IV-DNA complexes. We used resistance alleles and drug-target preferences to direct norfloxacin to topoisomerase IV and nalidixic acid to gyrase. We then found that the attack of topoisomerase IV inhibited DNA replication much more slowly than the attack of gyrase (Fig. 1and 2). A similar phenomenon has been seen with E. coli (27). With that organism, slow inhibition is likely to be due in part to topoisomerase IV functioning behind replication forks (27; reviewed in reference10), while rapid inhibition is likely to derive from action on gyrase ahead of forks (12).. The data presented above allow us to discern a ...

We have demonstrated that, in Escherichia coli, quinolone antimicrobial agents target topoisomerase IV (topo IV). The inhibition of topo IV becomes apparent only when gyrase is mutated to quinolone resistance. In such mutants, these antibiotics caused accumulation of replication catenanes, which is diagnostic of a loss of topo IV activity. Mutant forms of topo IV provided an additional 10-fold resistance to quinolones and prevented drug-induced catenane accumulation. Drug inhibition of topo IV differs from that of gyrase. (i) Wild-type topo IV is not dominant over the resistant allele. (ii) Inhibition of topo IV leads to only a slow stop in replication. (iii) Inhibition of topo IV is primarily bacteriostatic. These differences may result from topo IV acting behind the replication fork, allowing for repair of drug-induced lesions. We suggest that this and a slightly higher intrinsic resistance of topo IV make it secondary to gyrase as a quinolone target. Our results imply that the quinolone ...

Frequency quinolone-resistance alleles partitioned by phylogeny and environment. Depicted are the average frequencies with which gyrA/parC genes carry a quinolo

As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.

These bitmask values are appropriate for the following bitmasks used for SDSS-I and -II: LEGACY_TARGET2, SPECIAL_TARGET2 or SECTARGET.. ...

Type IIA topoisomerase (DNA gyrase/topo II, topoisomerase IV), A subunit; K11209 GSH-dependent disulfide-bond oxidoreductase [EC:1.8.4.-] ...

Type IIA topoisomerase (DNA gyrase/topo II, topoisomerase IV), A subunit; K11209 GSH-dependent disulfide-bond oxidoreductase [EC:1.8.4.-] ...

Also, in if_checks, the accepted variables are the basic ones (i,n,t,r,o,p,q). If a variable is referenced that doesnt exist, then the value is simply left blank or replaced with someone/something in output (i.e referring to $o when the trigger is: A kisses B). If variable $q has not been defined, it is automatically set to the last player that has triggered the program being executed (i.e. variable $n). Once $q has been defined, it can be modified with MOB REMEMBER and MOB FORGET commands in a program. Variable $q lets the mobile remember a player across different programs, which can be useful. Note that $q is set automatically only the FIRST TIME the mobile executes a program, every time thereafter it must be set with MOB REMEMBER.. The only problem with the variables is that the secondary object and the secondary target are passed by act() in the same location. This means that if you reference $t in an A puts B in C situation, the result will probably be a happy mud crash or some weird ...

Continuously deal 45,341 Shadowfrost damage every 1 sec to enemies in a cone in front of you. Deals reduced damage to secondary targets. You will continue breathing until your Runic Power is exhausted or you cancel the effect ...

Delight your skin with six of our popular formulas and save. CELL PARÉR MAXIMUM RENEWAL COMPLEX HERBAL WASH BALANCING LOTION FIRMING EYE CREAM STRESS TARGET FORMULA

1997) Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: Selective targeting of gyrase or topoisomerase IV by quinolones. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 41 (2). 471 - 474 (4). ISSN 0066-4804 ...

During its lifetime, a nucleus may be broken down or destroyed, either in the process of cell division or as a consequence of apoptosis (the process of programmed cell death). During these events, the structural components of the nucleus - the envelope and lamina - can be systematically degraded. In most cells, the disassembly of the nuclear envelope marks the end of the prophase of mitosis. However, this disassembly of the nucleus is not a universal feature of mitosis and does not occur in all cells. Some unicellular eukaryotes (e.g., yeasts) undergo so-called closed mitosis, in which the nuclear envelope remains intact. In closed mitosis, the daughter chromosomes migrate to opposite poles of the nucleus, which then divides in two. The cells of higher eukaryotes, however, usually undergo open mitosis, which is characterized by breakdown of the nuclear envelope. The daughter chromosomes then migrate to opposite poles of the mitotic spindle, and new nuclei reassemble around them. At a certain ...

Purpose. The occurrence of quinolone-resistance genes (qnrA, qnrB and qnrS), the presence of mutations in gyrA, gyrB and parC, as well as the expression of efflux pumps (acrB and acrF) and mutations in the gene ramR. Methodology. Were investigated in 30 bla KPC-2-positive isolates of Klebsiella pneumoniae taken from infection and colonization in hospital patients from Recife-PE, Brazil. The detection of the qnr, acrB and acrF genes and analysis of the mutations in ramR and the quinolone-resistance-determining regions of gyrA, gyrB and parC were performed by PCR followed by DNA sequencing. Results. Among the isolates analysed, 73.3 % (n=22) presented the qnrB gene. For the DNA sequencing, six isolates (K3-A2, K12-A2, K25-A2, K27-A2, K19-A2 and K3-C2) were selected and the qnrB1 and qnrB12 variants were detected. This is the first ever report, to the best of our knowledge, of the presence of qnrB12 in K. pneumoniae. This is also the first report, to the best of our knowledge, of the presence of qnrB1 or

Thank you for sharing this Antimicrobial Agents and Chemotherapy article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...

Replication of the DNA separating the opposing replication forks, leaves the completed chromosomes joined as catenanes or topologically interlinked circles. The circles are not covalently linked, but cannot be separated because they are interwound and each is covalently closed. The catenated circles require the action of topoisomerases to separate the circles [decatanation]. In E.coli, DNA topoisomerase IV plays the major role in the separation of the catenated chromosomes, transiently breaking both DNA strands of one chromosome and allowing the other chromosome to pass through the break. There has been some confusion about the role DNA gyrase plays in decatenation. To define the nomenclature, there are two types of topoisomerases: type I produces transient single-strand breaks in DNA and types II produces transient double-strand breaks. As a result, the type I enzyme removes supercoils from DNA one at a time, whereas the type II enzyme removes supercoils two at a time. The topo I of both ...

ID LEPCP_1_PE2621 STANDARD; PRT; 774 AA. AC LEPCP_1_PE2621; B1Y7E2; DT 00-JAN-0000 (Rel. 1, Created) DT 00-JAN-0000 (Rel. 2, Last sequence update) DT 00-JAN-0000 (Rel. 3, Last annotation update) DE SubName: Full=DNA topoisomerase IV, A subunit; (LEPCP_1.PE2621). GN OrderedLocusNames=Lcho_2632; OS LEPTOTHRIX CHOLODNII SP-6. OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales; Leptothrix. OX NCBI_TaxID=395495; RN [0] RP -.; RG -.; RL -.; CC -!- SEQ. DATA ORIGIN: Translated from the HOGENOM CDS LEPCP_1.PE2621. CC Leptothrix cholodnii SP-6, complete genome. CC complete sequence. CC -!- ANNOTATIONS ORIGIN:B1Y7E2_LEPCP CC -!- GENE_FAMILY: HOG000076277 [ FAMILY / ALN / TREE ] DR UniProtKB/Swiss-Prot; B1Y7E2; -. DR EMBL; CP001013; ACB34897.1; -; Genomic_DNA. DR RefSeq; YP_001791662.1; NC_010524.1. DR ProteinModelPortal; B1Y7E2; -. DR STRING; B1Y7E2; -. DR GeneID; 6160970; -. DR GenomeReviews; CP001013_GR; Lcho_2632. DR KEGG; lch:Lcho_2632; -. DR OMA; ILAITNE; -. DR ProtClustDB; PRK05561; -. ...

Other articles where Blastomere is discussed: animal development: Cleavage: …produced during cleavage are called blastomeres. The divisions are mitotic-i.e., each chromosome in the nucleus splits into two daughter chromosomes, so that the two daughter blastomeres retain the diploid number of chromosomes. During cleavage, almost no growth occurs between consecutive divisions, and the total volume of living matter does not…

In metaphase, two pairs of centrioles are aligned at opposite poles of the cell. Polar fibers from the pole have aligned the chromosomes at the metaphase plate. In anaphase the daughter chromosomes are pulled apart and begin moving to opposite poles of the cell. As the chromosomes near the pole their polar fibers become shorter. Polar fibers not connected to the chromosomes lengthen and elongate the cell.. ...

The cytoskeleton of a cell helps provide shape, strength, and an organised structure to the cell. The cytoskeleton can be compared to a transport network facilitating various types of movement in the cell. It helps with cell reproduction, the movement of organelles, the functions of muscles and intracellular transport between the organelles. It also enables the separation of daughter chromosomes to opposite poles during cell division.

Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.

There were few published studies of the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs or tests to be used as screening tests for detecting water-loss dehydration in older people. Therefore, to complete this review we sought, analysed and included raw datasets that included a reference standard and an index test in people aged ≥ 65 years.. We included three studies with published diagnostic accuracy data and a further 21 studies provided datasets that we analysed. We assessed 67 tests (at three cut-offs for each continuous outcome) for diagnostic accuracy of water-loss dehydration (primary target condition) and of current dehydration (secondary target condition).. Only three tests showed any ability to diagnose water-loss dehydration (including both impending and current water-loss dehydration) as stand-alone tests: expressing fatigue (sensitivity 0.71 (95% CI 0.29 to 0.96), specificity 0.75 (95% CI 0.63 to 0.85), in one study with 71 participants, but two ...

Primary Secondary found in: Primary And Secondary Target Groups Powerpoint Slide Introduction, 0814 Data Replication From Primary To Secondary Storage Media Representing Hard Drives Ppt Slides, Target Group Segmentation Ppt Ideas,..

Object. The aim of this study was to compare the effects of two different treatment protocols on physiological characteristics and outcome in patients with brain trauma. One protocol was primarily oriented toward reducing intracranial pressure (ICP), and the other primarily on maintaining cerebral perfusion pressure (CPP).. Methods. A series of 67 patients in Uppsala were treated according to a protocol aimed at keeping ICP less than 20 mm Hg and, as a secondary target, CPP at approximately 60 mm Hg. Another series of 64 patients in Edinburgh were treated according to a protocol aimed primarily at maintaining CPP greater than 70 mm Hg and, secondarily, ICP less than 25 mm Hg for the first 24 hours and 30 mm Hg subsequently.. The ICP and CPP insults were assessed as the percentage of monitoring time that ICP was greater than or equal to 20 mm Hg and CPP less than 60 mm Hg, respectively. Pressure reactivity in each patient was assessed based on the slope of the regression line relating mean ...

Thanks to Everett Brady, 405th, for submitting this mission report via Gerry Carpenter, both of whom participated in this attack. THE SECOND CHANCE AT KAGI. A second shot at Kagi, Formosa, was assigned the 405th may 22, 1944, specifically the railway yards at that fast decling center and Kizan Alcohol Plant designated as the secondary target. The usual striking force of 6 B-25s was dispatched 0815/I , with fifty six 250 pound 4 to 5 second delay para demos.. At target area, weather the density of jellied consomme was plunged into and quickly back out of as both targets were completely closed in. The sextet then proceeded to pounce upon targets of opportunity in two flights of three each. A butanol plant 10 miles SW of Kagi was attacked , 25 bombs falling in trains throughout the area, scoring hits on two large storage tanks resulting in large orage flame fires rising to a height of 200 feet, probably engulfing the entire area. A direct hit demolished a large warehouse but further damage ...

Download Off-Target Pipeline for free. OFF-TARGET PIPELINE is a platform intended to carry out a recently introduced chemical systems biology approach for secondary target identification, but may also be useful to other applications in bioinformatics and drug discovery.

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IV. 喉動態鏡檢查４主要用於了解聲帶振動狀況》由於喉動態鏡具有與聲帶振動頻率一致並同步的光源３檢查時可以觀察聲帶的振動方式３幅度等》正常情況下３發低音時３聲帶振動速度慢３振幅大４發高音時３聲帶振動速度快３振幅小４兩側聲帶呈對稱性３波浪形運動３聲帶振動速度均勻》聲帶有病變時３根據病情輕重３表現為振動速度變慢３振幅減少３聲帶波浪形運動減弱或消失３兩側常不對稱》 ...

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4GGL: Pyrrolopyrimidine inhibitors of dna gyrase b and topoisomerase iv, part i: structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity

A method for determining the best entry point for a percutaneous procedure, such as with a biopsy needle, comprises selecting first and second arbitrary entry points on a patient; determining the three dimensional (3-D) orientation of the needle at the first arbitrary entry point for pointing the needle at the primary target; determining the 3-D orientation of the needle at the first arbitrary entry point for pointing the needle at the secondary target; determining the 3-D dimensional orientation of the needle at the second arbitrary entry point for pointing the needle at the primary target; determining the 3-D orientation of the needle at the second arbitrary entry point for pointing the needle at the secondary target; determining a 3-D line representing the intersection of a first plane containing the first arbitrary entry point, the primary target point, and the secondary target point, and a second plane containing the second arbitrary entry point, the primary target, and the secondary target point,

effect the world around them Just under 64 million women ages 25-55 in the United States Just under 21 million women ages 14-24 in the United States Goals Objectives Increase product awareness among primary and secondary target markets Increase product awareness among primary and secondary target markets Obtain customer feedback to generate new and improved product ideas. Ensure that potential consumers are aware of Lush Cosmetics creative and innovative solutions to make a positive impact on the planet Maintain affordability in order to continually produce a high sales volume Maintain Lush Cosmetics commitment to a policy that refuses testing products and ingredients on animals Contniue to utilize Lush Cosmetics innovative marketing strategies and product development approach Promote the benefits of using natural products in cosmetics rather than artificial preservatives Promote Lush Cosmetics ethical campaigns such as, Save our Seals, No Nukes, and Saving Sharks Around the World To ...

The increasing amount of heavy metals used in manufacturing equivalently increases hazards of environmental pollution by industrial products such as cadmium oxide (CdO) nanoparticles. Here, we aimed to unravel the CdO nanoparticle destiny upon their entry into lungs by inhalations, with the main focus on the ultrastructural changes that the nanoparticles may cause to tissues of the primary and secondary target organs. We indeed found the CdO nanoparticles to be transported from the lungs into secondary target organs by blood. In lungs, inhaled CdO nanoparticles caused significant alterations in parenchyma tissue including hyperemia, enlarged pulmonary septa, congested capillaries, alveolar emphysema and small areas of atelectasis. Nanoparticles were observed in the cytoplasm of cells lining bronchioles, in the alveolar spaces as well as inside the membranous pneumocytes and in phagosomes of lung macrophages. Nanoparticles even penetrated through the membrane into some organelles including mitochondria

8:35 Using Dose Responses to Identify Multiple Activities of Kinase Inhibitors. Petra Ross-McDonald, Ph.D., Senior Research Investigator, Bristol-Myers Squibb Co.. Multi-target pharmacology is recognized and investigated more aggressively for kinase inhibitors than for most other pharmaceutical targets. I will present two aspects of characterizing multi-target biology. The first is a successful mechanism of action study that analyzed a LIMK inhibitor series with an unknown secondary target: our unexpected findings shake common assumptions about the off-target effects of kinase inhibitors. Dose responses were key to this investigation of multi-target biology, and IC50 values from bioassays are a central currency of drug discovery. For compounds that hit multiple targets with differing IC50s, separating the distinct responses is necessary to make realistic connections between targets and biology. In the second part of my talk, Ill present new methods that for the first time allow routine ...

Finafloxacin dosed for 5 days was as efficient as finafloxacin dosed for 10 days in a combined evaluation of the clinical and microbiological response with efficacy rates of 70% and 68% on day 17 of the study. Both finafloxacin dosing regimens were more efficient than the treatment with ciprofloxacin for 10 days resulting in 57% efficacy. The short 5 day treatment period with finafloxacin did not result in an increased rate of relapses when compared to both 10 day treatment regimens in this study ...

Salmonella enterica infections are common causes of bloodstream infection in low-resource areas, where they may be difficult to distinguish from other febrile illnesses and may be associated with a high case fatality ratio. Microbiologic culture of blood or bone marrow remains the mainstay of laboratory diagnosis. Antimicrobial resistance has emerged in Salmonella enterica, initially to the traditional first-line drugs chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole. Decreased fluoroquinolone susceptibility and then fluoroquinolone resistance have developed in association with chromosomal mutations in the quinolone resistance-determining region of genes encoding DNA gyrase and topoisomerase IV and also by plasmid-mediated resistance mechanisms. Resistance to extended-spectrum cephalosporins has occurred more often in nontyphoidal than in typhoidal Salmonella strains. Azithromycin is effective for the management of uncomplicated typhoid fever and may serve as an alternative oral ...

In this study, the prevalence of plasmid-mediated quinolone resistance (PMQR) was investigated in 495 Escherichia coli isolates from diseased food-producing animals in Guangdong province, China. The quinolone resistance-determining regions (QRDRs) of the gyrA and parC genes were analysed for mutations in 55 isolates harbouring only oqxAB and all isolates harbouring other PMQR genes. Overall, 282 (57.0 %) E. coli isolates had at least one PMQR gene. oqxAB was detected in 215 isolates and predominated the PMQR genes, followed by qnrS (63 isolates), aac(6′)-Ib-cr (56 isolates), qnrB (39 isolates) and qepA (18 isolates). qnrA, qnrC and qnrD were not found in any of the isolates. The rates of resistance to ciprofloxacin, enrofloxacin, levofloxacin and nalidixic acid were 75.2, 81.0, 70.5 and 97.4 %, respectively, among the 495 isolates. Eight types of mutation in gyrA were detected in 154 PMQR-positive isolates, and 147 isolates were found to have mutations in parC. PFGE analysis indicated that the PMQR

During the 1990s, multidrug-resistant tuberculosis (MDR-TB), resistant to at least isoniazid and rifampin, emerged as a great threat to global tuberculosis (TB) control [1]. For most MDR-TB patients, the World Health Organization (WHO) recommends a treatment regimen including second-line anti-TB drugs [2]. One of the most effective second-line drugs is fluoroquinolone [3]. During the treatment, MDR-TB may develop resistance to fluoroquinolone, or even become extensively drug-resistant (XDR-TB), which is resistant to both fluoroquinolone and at least one of three injectable second-line drugs [4]. The main genetic mechanism of fluoroquinolone resistance lies in the mutations in the quinolone-resistance-determining region of gyrA and gyrB [5]. ...

Streptococcus suis rexA, pec1, parE, pec2, fic, pec3, pec4, parC, pec5, ilvE genes for ATP-dependent exonuclease/helicase subunit A, hypothetical protein, topoisomerase IV subunit B, hypothetical, mobilization/filamentation protein, hypothetical protein, hypothetical protein, topoisomerase IV subunit A, hypothetical protein, branched-chain amino acid aminotransferase, partial and complete ...

Streptococcus suis rexA, pec1, parE, pec2, fic, pec3, pec4, parC, pec5, ilvE genes for ATP-dependent exonuclease/helicase subunit A, hypothetical protein, topoisomerase IV subunit B, hypothetical, mobilization/filamentation protein, hypothetical protein, hypothetical protein, topoisomerase IV subunit A, hypothetical protein, branched-chain amino acid aminotransferase, partial and complete ...

Product Name: Gatifloxacin Eye Drops. Common Name: Genteal, Genteal Mild, Gonak, Goniosoft, Goniovisc. Strength: 0.5%. Description: Gatifloxacin sold under the brand names Gatiflo, Tequin and Zymar, is an antibiotic of the fourth-generation fluoroquinolone family, that like other members of that family, inhibits the bacterial enzymes DNA gyrase and topoisomerase IV. Indications and Usage:. Gatifloxacin ophthalmic solution, 0.5% is indicated for the treatment of bacterial conjunctivitis caused by susceptible strains of the following organisms:. Aerobic gram-positive bacteria:. ...

Paclitaxel is a commonly used drug in treating cancers including breast, lung, and pancreatic. Paclitaxel acts as a MAP and stabilizes the MT from the inside and decreases the dynamic instability of the MT. Due to the lack of dynamic instability, paclitaxel treated cells are unlikely to successfully complete mitosis. The cell is unable to transition from metaphase with the chromosomes lined up in the center of the cell to anaphase where the MT are pulling the daughter chromosome to opposite sides of the cell. Without mitosis, the cell is unable to divide and the cancerous cells cannot proliferate as quickly. After several unsuccessful attempts of undergoing mitosis, the cell undergoes apoptosis [7]. Figure 7 shows images comparing the stages of mitosis in an untreated cell with a paclitaxel treated cell and a cell treated with another MT targeting molecule, vinflunine. Cells can become resistant to paclitaxel due to cells attempting to overcompensate for the lack of dynamic instability. The MT ...

Genetic studies, in Drosophila as well as vertebrates, have shown that the zinc finger containing Gli family of proteins is the primary mediator of Hh-dependent transcriptional regulation of target genes in responding cells (Ingham and McMahon 2001; Hooper and Scott 2005). It is now largely accepted that Hh modulates target gene transcription by inhibiting the formation of the proteolytically processed transcriptional repressor form of Gli, Glirep, and by promoting the accumulation of the transcriptional activator variant, Gliact, in the nucleus (Ingham and McMahon 2001; Hooper and Scott 2005). Therefore, genes that are transcriptionally activated due to the loss of Glirep and/or the generation of Gliact can be classified as direct targets of the Hh pathway. If a direct target gene encodes a transcriptional regulator it can, in turn, activate or repress many other downstream target genes. These downstream genes are indirect or secondary targets of Hh signaling. In our microarray-based screen for ...

The risk assessment of nanomaterials is a challenge. The Nano-Guidance (SCCS/1484/12) covers the essential elements that would be required in a safety dossier on manufactured nanomaterial, i.e. physicochemical characterization, toxicological evaluation, exposure assessment, and risk characterization. Further notes in relation to nanomaterials are provided in the SCCS Notes of Guidance (SCCS/1501/12). It is crucial when assessing possible risks associated with nanoparticles to consider their uptake. It is primarily for the insoluble particles that health concerns related to possible uptake may arise. Should they become systemically available, translocation/ transportation and eventual accumulation in secondary target organs may occur ...

Buru Energy has observed hydrocarbon shows after intersecting the secondary target Anderson Formation at its Adoxa-1 conventional oil exploration well in the Canning Basin, Western Australia. The significance of these individual sand bodies with hydrocarbon shows in cuttings samples will be evaluated with wireline logs once the well is completed to its total planned depth of

TY - JOUR. T1 - Structural basis for suppression of hypernegative DNA supercoiling by E. coli topoisomerase I. AU - Tan, Kemin. AU - Zhou, Qingxuan. AU - Cheng, Bokun. AU - Zhang, Zhongtao. AU - Joachimiak, Andrzej. AU - Tse-Dinh, Yuk Ching. PY - 2015/12. Y1 - 2015/12. N2 - Escherichia coli topoisomerase I has an essential function in preventing hypernegative supercoiling of DNA. A full length structure of E. coli topoisomerase I reported here shows how the C-terminal domains bind single-stranded DNA (ssDNA) to recognize the accumulation of negative supercoils in duplex DNA. These C-terminal domains of E. coli topoisomerase I are known to interact with RNA polymerase, and two flexible linkers within the C-terminal domains may assist in the movement of the ssDNA for the rapid removal of transcription driven negative supercoils. The structure has also unveiled for the first time how the 4-Cys zinc ribbon domain and zinc ribbon-like domain bind ssDNA with primarily-stacking interactions. This novel ...

Topoisomerases are ubiquitous enzymes necessary for controlling the interlinking and twisting of DNA molecules. Among the four topoisomerases identified in eubacteria, two, DNA gyrase and topoisomerase IV, have been exploited by nature and the pharmaceutical industry as antibacterial targets. Natural products that are inhibitors of one or both of these topoisomerases include the coumarin and cyclothialidine classes, which interfere with adenosine triphosphate hydrolysis, cinodine, flavones, and terpenoid derivatives. The plasmid-encoded bacterial peptides microcin B17 and CcdB also inhibit DNA gyrase. The quinolones, a synthetic class of antibacterials that act on both DNA gyrase and topoisomerase IV, have had the broadest clinical applications, however. Quinolone congeners differ in their relative potencies for DNA gyrase and topoisomerase IV. Studies of an expanding set of resistant mutant enzymes and the crystal structure of the homologous enzyme in yeast have contributed to our understanding ...

TY - JOUR. T1 - Emergence of fluoroquinolone-resistant Streptococcus pyogenes in Japan by a point mutation leading to a new amino acid substitution. AU - Arai, Kazuaki. AU - Hirakata, Yoichi. AU - Yano, Hisakazu. AU - Kanamori, Hajime. AU - Endo, Shiro. AU - Hirotani, Ayako. AU - Abe, Yuko. AU - Nagasawa, Mitsuaki. AU - Kitagawa, Miho. AU - Aoyagi, Tetsuji. AU - Hatta, Masumitsu. AU - Yamada, Mitsuhiro. AU - Nishimaki, Katsushi. AU - Takayama, Yoko. AU - Yamamoto, Natsuo. AU - Kunishima, Hiroyuki. AU - Kaku, Mitsuo. PY - 2011/3/1. Y1 - 2011/3/1. N2 - Objectives: Streptococcus pyogenes causes various diseases in humans. While the prevalence of fluoroquinolone-resistant S. pyogenes isolates has been increasing since 2000 in the USA and Europe, it has remained very low in Japan. We isolated a fluoroquinolone-resistant S. pyogenes strain and analysed its genetics. Methods: TU-296, a strain of S. pyogenes resistant to levofloxacin (MIC 16 mg/L), was isolated from the throat of a patient in their ...

Among 4,215 Streptococcus pneumoniae isolates obtained in Spain during 2006, 98 (2.3%) were ciprofloxacin resistant (3.6% from adults and 0.14% from children). In comparison with findings from a 2002 study, global resistance remained stable. Low-level resistance (30 isolates with MIC 4-8 μg/mL) was caused by a reserpine-sensitive efflux phenotype (n = 4) or single topoisomerase IV (parC [n = 24] or parE [n = 1]) changes. One isolate did not show reserpine-sensitive efflux or mutations. High-level resistance (68 isolates with MIC ≥16 μg/mL) was caused by changes in gyrase (gyrA) and parC or parE. New changes in parC (S80P) and gyrA (S81V, E85G) were shown to be involved in resistance by genetic transformation. Although 49 genotypes were observed, clones Spain9V-ST156 and Sweden15A-ST63 accounted for 34.7% of drug-resistant isolates. In comparison with findings from the 2002 study, clones Spain14-ST17, Spain23F-ST81, and ST8819F decreased and 4 new genotypes (ST9710A, ST57016, ST43322, and ST71733)

Alterations in the target proteins of fluoroquinolones, especially in GyrA and ParC, are known to cause resistance. Here, we investigated environmental Escherichia communities to explore the possible link between the abundance of mutations, and the exposure to fluoroquinolones. Sediment samples were collected from a relatively pristine lake, up and downstream from a sewage treatment plant, and from several industrially polluted sites. The quinolone resistance-determining regions of gyrA and parC were analyzed using amplicon sequencing of metagenomic DNA. Five non-synonymous substitutions were present in all samples, and all of these mutations have been previously linked to fluoroquinolone resistance in Escherichia coli. In GyrA, substitutions S83L and D87N were on average detected at frequencies of 86 and 32%, respectively, and 31% of all amplicons encoded both substitutions. In ParC, substitutions S80I, E84G, and E84V were detected in 42, 0.9, and 6.0% of the amplicons, respectively, and 6.5% ...

Trovafloxacin is a broad spectrum antibiotic that inhibits DNA supercoiling in various bacteria by blocking the activity of DNA gyrase and topoisomerase IV. It is not used widely due to the risk of hepatotoxicity. It tends to have better gram-positive bacterial coverage and less gram-negative coverage than the previous fluoroquinolones. Mechanism of action of fluoroquinolones including trovafloxacin is different from that of penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines. Therefore fluoroquinolones may be active against pathogens that are resistant to these antibiotics. There is no cross-resistance between trovafloxacin and the mentioned classes of antibiotics. The overall results obtained from in vitro synergy studies, testing combinations of trovafloxacin with beta-lactams and aminoglycosides, indicate that synergy is strain specific and not commonly encountered. This agrees with results obtained previously with other fluoroquinolones. Resistance to trovafloxacin ...

Resistance to quinolones can develop rapidly, even during a course of treatment. Numerous pathogens, including Staphylococcus aureus, enterococci, and Streptococcus pyogenes now exhibit resistance worldwide.[3] Widespread veterinary usage of quinolones, in particular in Europe, has been implicated. There are three known mechanisms of resistance.[4] Efflux pumps can be used to decrease intracellular drug concentration. In gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drug effectiveness. ...

a national communication strategy is key to a national policy response, and this must rest on acknowledging two things - one, behaviour change communication is a specialised field whose expertise must be harnessed, and two, the nature of reproductive decision-making in India is changing along with immense changes in the Indian family structure. A communication strategy needs to identify primary targets (decision-makers) and secondary targets (decision supporters), and reach them through strategic media platforms - traditional, conventional and new media. As for the core content of messages, a lot can be said, but for now let us agree to go beyond billboard exhortations to love the girl child. And recognise that the girl will grow up to be a woman one day. ...

Several people have recently asked me if I know of anyone who is researching cures for fluoroquinolone toxicity. The short answer is, no, unfortunately, I dont know of any individuals, institutions, or organizations that are working to find a cure for fluoroquinolone toxicity. The longer answer is a bit more complex and nuanced. In order to get doctors…

Several people have recently asked me if I know of anyone who is researching cures for fluoroquinolone toxicity. The short answer is, no, unfortunately, I dont know of any individuals, institutions, or organizations that are working to find a cure for fluoroquinolone toxicity. The longer answer is a bit more complex and nuanced. In order to get doctors…

Born Syd-ney, Aus-tralia 1945 Lives and works in Sydney Inter-ro-gat-ing for-mal and cul-tur-al ortho-dox-ies, the vast and uncom-pro-mis-ing prac-tice of Mike Parr assumes mul-ti-ple forms through a con-fla-tion of draw-ing, print-mak-ing, sculp-ture and per-for-mance. Explor-ing the lim-its of his phys-i-cal and men-tal capac-i-ty, Parrs high-ly influ-en-tial per-for-mance prac-tice employs his own body as a means to exam-ine […]

Bompas & Parr, - the jellymongers extraordinaire talk about their often outrageous blend of art, food and sensuality thats proving a recipe for success.