5,550 results match your criteria gyrase


Shared and Unique Evolutionary Trajectories to Ciprofloxacin Resistance in Gram-Negative Bacterial Pathogens.

mBio 2021 06 22;12(3):e0098721. Epub 2021 Jun 22.

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

Resistance to the broad-spectrum antibiotic ciprofloxacin is detected at high rates for a wide range of bacterial pathogens. To investigate the dynamics of ciprofloxacin resistance development, we applied a comparative resistomics workflow for three clinically relevant species of Gram-negative bacteria: Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa. We combined experimental evolution in a morbidostat with deep sequencing of evolving bacterial populations in time series to reveal both shared and unique aspects of evolutionary trajectories. Read More

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Properties of with a deleted apicoplast DNA gyrase.

Antimicrob Agents Chemother 2021 Jun 21:AAC0058621. Epub 2021 Jun 21.

Department of Chemistry, University of Washington, Seattle, Washington, USA.

Malaria parasites have three genomes: a nuclear genome, a mitochondrial genome, and an apicoplast genome. Since the apicoplast is a plastid organelle of prokaryotic origin and has no counterpart in the human host, it can be a source of novel targets for antimalarials. DNA gyrase (Gyr) A and B subunits both have apicoplast-targeting signals. Read More

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Electron microscopy reveals unexpected cytoplasm and envelope changes during thymineless death in .

J Bacteriol 2021 Jun 21:JB0015021. Epub 2021 Jun 21.

Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Bacterial rod-shaped cells experiencing irreparable chromosome damage should filament without other morphological changes. Thymineless death (TLD) strikes thymidine auxotrophs denied external thymine/thymidine (T) supplementation. Such T-starved cells cannot produce the DNA precursor dTTP and therefore stop DNA replication. Read More

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Novel chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids as potential antibacterial repressors against methicillin-resistant Staphylococcus aureus.

Eur J Med Chem 2021 Jun 9;222:113628. Epub 2021 Jun 9.

Sauvage Laboratory for Smart Materials, Harbin Institute of Technology (Shenzhen), Shenzhen, 518055, China; Shenzhen Key Laboratory of Flexible Printed Electronics Technology, School of Materials Science and Engineering, Harbin Institute of Technology, Shenzhen, 518055, China. Electronic address:

The increasing resistance of methicillin-resistant Staphylococcus aureus (MRSA) to antibiotics has led to a growing effort to design and synthesize novel structural candidates of chalcone-conjugated, multi-flexible end-group coumarin thiazole hybrids with outstanding bacteriostatic potential. Bioactivity screening showed that hybrid 5i, which was modified with methoxybenzene, exerted a significant inhibitory activity against MRSA (MIC = 0.004 mM), which was 6 times better than the anti-MRSA activity of the reference drug norfloxacin (MIC = 0. Read More

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Topoisomerase I Essentiality, DnaA-independent Chromosomal Replication, and Transcription-Replication Conflict in .

J Bacteriol 2021 Jun 14:JB0019521. Epub 2021 Jun 14.

Laboratory of Bacterial Genetics, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.

Topoisomerase I (Topo I) of , encoded by , acts to relax negative supercoils in DNA. Topo I deficiency results in hypernegative supercoiling, formation of transcription-associated RNA-DNA hybrids (R-loops), and DnaA- and -independent constitutive stable DNA replication (cSDR), but some uncertainty persists as to whether is essential for viability in and related enterobacteria. Here we show that several alleles, including Δ, confer lethality in derivatives of wild-type strain MG1655. Read More

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Anti-MRSA drug discovery by ligand-based virtual screening and biological evaluation.

Bioorg Chem 2021 Jun 3;114:105042. Epub 2021 Jun 3.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address:

S. aureus resistant to methicillin (MRSA) is one of the most-concerned multidrug resistant bacteria, due to its role in life-threatening infections. There is an urgent need to develop new antibiotics against MRSA. Read More

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Archaea: A Gold Mine for Topoisomerase Diversity.

Front Microbiol 2021 25;12:661411. Epub 2021 May 25.

Département de biologie, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), École normale supérieure, CNRS, INSERM, Université PSL, Paris, France.

The control of DNA topology is a prerequisite for all the DNA transactions such as DNA replication, repair, recombination, and transcription. This global control is carried out by essential enzymes, named DNA-topoisomerases, that are mandatory for the genome stability. Since many decades, the Archaea provide a significant panel of new types of topoisomerases such as the reverse gyrase, the type IIB or the type IC. Read More

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Identification of new building blocks by fragment screening for discovering GyrB inhibitors.

Bioorg Chem 2021 May 31;114:105040. Epub 2021 May 31.

Research Center for Drug Discovery and Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address:

DNA gyrase is an essential DNA topoisomerase that exists only in bacteria. Since novobiocin was withdrawn from the market, new scaffolds and new mechanistic GyrB inhibitors are urgently needed. In this study, we employed fragment screening and X-ray crystallography to identify new building blocks, as well as their binding mechanisms, to support the discovery of new GyrB inhibitors. Read More

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Rational design, synthesis and testing of novel tricyclic topoisomerase inhibitors for the treatment of bacterial infections part 1.

RSC Med Chem 2020 Dec 18;11(12):1366-1378. Epub 2020 Sep 18.

Redx Anti-Infectives Ltd, Alderley Park, Mereside Macclesfield SK10 4TG UK.

The alarming reduction in drug effectiveness against bacterial infections has created an urgent need for the development of new antibacterial agents that circumvent bacterial resistance mechanisms. We report here a series of DNA gyrase and topoisomerase IV inhibitors that demonstrate potent activity against a range of Gram-positive and selected Gram-negative organisms, including clinically-relevant and drug-resistant strains. In part 1, we present a detailed structure activity relationship (SAR) analysis that led to the discovery of our previously disclosed compound, REDX05931, which has a minimum inhibitory concentration (MIC) of 0. Read More

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December 2020

Pharmacodynamic Evaluation of Dosing, Bacterial Kill, and Resistance Suppression for Zoliflodacin Against in a Dynamic Hollow Fiber Infection Model.

Front Pharmacol 2021 21;12:682135. Epub 2021 May 21.

WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

Antimicrobial resistance in is threatening the treatment and control of gonorrhea globally, and new treatment options are imperative. Utilizing our dynamic hollow fiber infection model (HFIM), we examined the pharmacodynamics of the first-in-class spiropyrimidinetrione (DNA gyrase B inhibitors), zoliflodacin, against the reference strains World Health Organization F (susceptible to all relevant antimicrobials) and WHO X (extensively drug resistant, including resistance to ceftriaxone) over 7 days. Dose-range experiments with both strains, simulating zoliflodacin single oral dose regimens of 0. Read More

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Azithromycin and Ciprofloxacin Can Promote Antibiotic Resistance in Biosolids and Biosolids-Amended Soils.

Appl Environ Microbiol 2021 Jul 27;87(16):e0037321. Epub 2021 Jul 27.

Interdisciplinary Center for Biotechnology Research (ICBR), University of Floridagrid.15276.37, Gainesville, Florida, USA.

Spread of biosolids-borne antibiotic resistance is a growing public and environmental health concern. Herein, we conducted incubation experiments involving biosolids, which are byproducts of sewage treatment processes, and biosolids-amended soil. Quantitative reverse transcription-PCR (RT-qPCR) was employed to assess responses of select antibiotic resistance genes (ARGs) and mobile elements to environmentally relevant concentrations of two biosolids-borne antibiotics, azithromycin (AZ) and ciprofloxacin (CIP). Read More

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Interaction of Quinolones Carrying New R1 Group with DNA Gyrase.

Microb Drug Resist 2021 Jun 1. Epub 2021 Jun 1.

Division of Bioresources, Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan.

Leprosy is a chronic infectious disease caused by and the treatment of choice is ofloxacin (OFX). Specific amino acid substitutions in DNA gyrase of have been reported leading to resistance against the drug. In our previous study, WQ-3810, a fluoroquinolone with a new R1 group (6-amino-3,5-difluoropyridin-2-yl) was shown to have a strong inhibitory activity on OFX-resistant DNA gyrases of , and the structural characteristics of its R1 group was predicted to enhance the inhibitory activity. Read More

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Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains.

Antibiotics (Basel) 2021 May 13;10(5). Epub 2021 May 13.

Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain.

Antibiotic resistance in has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Read More

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Interactions with Microbial Proteins Driving the Antibacterial Activity of Flavonoids.

Pharmaceutics 2021 May 5;13(5). Epub 2021 May 5.

Department of Medicine and Surgery, University of Salerno, 84082 Baronissi, Italy.

Flavonoids are among the most abundant natural bioactive compounds produced by plants. Many different activities have been reported for these secondary metabolites against numerous cells and systems. One of the most interesting is certainly the antimicrobial, which is stimulated through various molecular mechanisms. Read More

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Novel 6-hydroxyquinolinone derivatives: Design, synthesis, antimicrobial evaluation, in silico study and toxicity profiling.

J Comput Chem 2021 Aug 26;42(22):1561-1578. Epub 2021 May 26.

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Port Said University, Port Said, Egypt.

Infectious diseases of bacteria and fungi have become a major risk to public health because of antibiotic and antifungal resistance. However, the availability of effective antibacterial and antifungal agents is becoming increasingly limited with growing resistance to existing drugs. In response to that, novel agents are critically needed to overcome such resistance. Read More

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Microwave assisted one-pot synthesis, photophysical and physicochemical studies of novel biologically active heterocyclic Donor (D)-π-Acceptor (A) chromophore.

Bioorg Chem 2021 Jul 5;112:104964. Epub 2021 May 5.

Department of Chemistry, Faulty of Science, University of Tabuk, Tabuk, Saudi Arabia.

A donor-π-acceptor (D-π-A) chromophore, 2-amino-4-(9-ethyl-9H-carbazol-3-yl)-8-methoxy-5,6-dihydrobenzo[h]quinoline-3-carbonitrile (AEDQ) was synthesized from the condensation of 6-methoxy-3,4-dihydronaphthalen-1(2H)-one, 9-ethyl-9H-carbazole-3-carbaldehyde, malononitrile and NHOAc in ethanol. Spectroscopic techniques and elemental analysis were employed to establish the structure of AEDQ. Photophysical parameters and fluorescence quantum yield were calculated in the different polarity solvents to evaluate the interactions of the solvent with AEDQ chromophore. Read More

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Molecular dynamics simulation of bioactive compounds of leaf extract as DNA gyrase inhibitor.

J Biomol Struct Dyn 2021 May 21:1-8. Epub 2021 May 21.

School of Pharmacy, St. John's University of Tanzania, Dodoma, Tanzania.

Medicinal plants have served humans as medicine for centuries. (L.) (Ashwagandha) leaf extract is traditionally used in managing and treating bacterial infections. Read More

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Piperidine-4-Carboxamides Target DNA Gyrase in Mycobacterium abscessus.

Antimicrob Agents Chemother 2021 Jul 16;65(8):e0067621. Epub 2021 Jul 16.

Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, New Jersey, USA.

New, more-effective drugs for the treatment of lung disease caused by nontuberculous mycobacteria (NTM) are needed. Among NTM opportunistic pathogens, Mycobacterium abscessus is the most difficult to cure and intrinsically multidrug resistant. In a whole-cell screen of a compound collection active against Mycobacterium tuberculosis, we previously identified the piperidine-4-carboxamide (P4C) MMV688844 (844) as a hit against M. Read More

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Phosphorus-nitrogen compounds: part 53-synthesis, characterization, cytotoxic and antimicrobial activity, DNA interaction and molecular docking studies of new mono- and dispirocyclotriphosphazenes with pendant arm(s).

Mol Divers 2021 May 14. Epub 2021 May 14.

Department of Physics, Hacettepe University, 06800, Ankara, Turkey.

Mono-/dispirocyclotriphosphazenes with pendant arm(s) are robust, but they are less investigated inorganic ring systems. In this study, a series of mono (3 and 4)- and dispirocyclotriphosphazenes with 4-chloro-benzyl pendant arm(s) (13-16) was obtained from the Cl exchange reactions of hexachlorocyclotriphosphazene with sodium (N-benzyl)aminopropanoxides (1 and 2). When compound (3) reacted with excess pyrrolidine, morpholine, tetra-1,4-dioxa-8-azaspiro[4,5]decane (DASD) and piperidine, the fully substituted monospirocyclotriphosphazenes (7, 9, 10 and 12) occurred. Read More

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Molecular docking analysis and evaluation of the antibacterial and antioxidant activities of the constituents of Ocimum cufodontii.

Sci Rep 2021 May 12;11(1):10101. Epub 2021 May 12.

Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, P.O.Box 1888, Adama, Ethiopia.

Ocimum cufodontii ((Lanza) A.J.Paton) has been traditionally used in Ethiopia against bacteria. Read More

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Semisynthesis, Antiplasmodial Activity, and Mechanism of Action Studies of Isocoumarin Derivatives.

J Nat Prod 2021 05 12;84(5):1434-1441. Epub 2021 May 12.

Center of Cellular and Molecular Biology of Diseases, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, City of Knowledge, Clayton, Apartado 0816-02852, Panama.

In this study, eight natural isocoumarins (-) were isolated from a marine-derived sp. fungus. To explore their structure-activity relationship and discover potent antimalarial leads, a small library of 22 new derivatives (-, , -, -, and ) were semisynthesized by varying the substituents of the aromatic ring and the aliphatic side chains. Read More

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Impact of Bi Doping into Boron Nitride Nanosheets on Electronic and Optical Properties Using Theoretical Calculations and Experiments.

Nanoscale Res Lett 2021 May 12;16(1):82. Epub 2021 May 12.

Department of Physics, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa, 31982, Saudi Arabia.

In the present work, boron nitride (BN) nanosheets were prepared through bulk BN liquid phase exfoliation while various wt. ratios (2.5, 5, 7. Read More

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Unraveling the binding mechanism of an Oxovanadium(IV) - Curcumin complex on albumin, DNA and DNA gyrase by in vitro and in silico studies and evaluation of its hemocompatibility.

J Inorg Biochem 2021 Aug 24;221:111402. Epub 2021 Feb 24.

Laboratory of Biochemistry, Department of Chemistry, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece. Electronic address:

An oxovanadium(IV) - curcumin based complex, viz. [VO(cur)(2,2´-bipy)(HO)] where cur is curcumin and bipy is bipyridine, previously synthesized, has been studied for interaction with albumin and DNA. Fluorescence emission spectroscopy was used to evaluate the interaction of the complex with bovine serum albumin (BSA) and the BSA-binding constant (K) was calculated to be 2. Read More

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Synthesis, antimicrobial, anti-cancer and in silico studies of new urea derivatives.

Bioorg Chem 2021 Jul 29;112:104953. Epub 2021 Apr 29.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Sadat City, Menoufia, Egypt.

The reaction of an alkyl or aryl isocyanates with some primary amines in acetonitrile at room temperature afforded the corresponding alkyl- and aryl-urea derivatives. All the prepared urea compounds have been elucidated by FTIR, NMR, and elemental analysis. The compounds 1 and 3 were confirmed by single-crystal X-ray diffraction. Read More

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Antibacterial and antioxidant activities of extracts and isolated compounds from the roots extract of Cucumis prophetarum and in silico study on DNA gyrase and human peroxiredoxin 5.

BMC Chem 2021 May 6;15(1):32. Epub 2021 May 6.

Department of Applied Chemistry, School of Applied Natural Science, Adama Science and Technology University, P.O.Box 1888, Adama, Ethiopia.

Background: Cucumis prophetarum is traditionally used to treat liver and lung disorders, heart failure, diarrhea, gonorrhea, skin infections, intestinal problems and cancer. In the present work, the isolation of two novel compounds along with their antibacterial and antioxidant activities is reported for the first time.

Methods: Silica gel column chromatography was applied to separate constituents of the roots of C. Read More

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Identifying potential candidate Culicoides spp. for the study of interactions with Candidatus Cardinium hertigii.

Med Vet Entomol 2021 May 6. Epub 2021 May 6.

Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, U.K.

Culicoides biting midges (Diptera: Ceratopogonidae) are vectors responsible for the transmission of several viruses of veterinary importance. Previous screens of Culicoides have described the presence of the endosymbiont Candidatus Cardinium hertigii (Bacteroidetes). However, any impacts of this microbe on vectorial capacity, akin to those conferred by Wolbachia in mosquitoes, are yet to be uncovered and await a suitable system to study Cardinium-midge interactions. Read More

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Discovery and Optimization of DNA Gyrase and Topoisomerase IV Inhibitors with Potent Activity against Fluoroquinolone-Resistant Gram-Positive Bacteria.

J Med Chem 2021 05 30;64(9):6329-6357. Epub 2021 Apr 30.

Piramal Discovery Solutions, Pharmaceutical Special Economic Zone, Sarkhej Bavla Highway, Ahmedabad, Gujarat 382213, India.

Herein, we describe the discovery and optimization of a novel series that inhibits bacterial DNA gyrase and topoisomerase IV binding to, and stabilization of, DNA cleavage complexes. Optimization of this series led to the identification of compound , which has potent activity against Gram-positive bacteria, a favorable safety profile, and excellent pharmacokinetic properties. Compound was found to be efficacious against fluoroquinolone-sensitive infection in a mouse thigh model at lower doses than moxifloxacin. Read More

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Effectiveness of Bioactive Compound as Antibacterial and Anti-Quorum Sensing Agent from : An In Silico Study.

Molecules 2021 Apr 23;26(9). Epub 2021 Apr 23.

Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Padjadjaran, Sumedang 45363, Indonesia.

Background: antibiotic resistance encourages the development of new therapies, or the discovery of novel antibacterial agents. Previous research revealed that (Sarang Semut) contain potential antibacterial agents. However, specific proteins inhibited by them have not yet been identified as either proteins targeted by antibiotics or proteins that have a role in the quorum-sensing system. Read More

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Design, Synthesis, and Antibacterial Screening of Some Novel Heteroaryl-Based Ciprofloxacin Derivatives as DNA Gyrase and Topoisomerase IV Inhibitors.

Pharmaceuticals (Basel) 2021 Apr 22;14(5). Epub 2021 Apr 22.

Department of Chemistry, Faculty of Science, Sohag University, Sohag 82524, Egypt.

A novel series of ciprofloxacin hybrids comprising various heterocycle derivatives has been synthesized and structurally elucidated using H NMR, C NMR, and elementary analyses. Using ciprofloxacin as a reference, compounds were screened in vitro against Gram-positive bacterial strains such as and and Gram-negative strains such as and . As a result, many of the compounds examined had antibacterial activity equivalent to ciprofloxacin against test bacteria. Read More

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Antimicrobial Susceptibility Pattern of spp. Isolated from Enteric Fever Patients in Nepal.

Infect Dis Rep 2021 Apr 21;13(2):388-400. Epub 2021 Apr 21.

Central Department of Microbiology, Tribhuvan University, Kirtipur, Kathmandu 44618, Nepal.

Introduction: Enteric fever, a systemic infection caused by Typhi and Paratyphi is one of the most common infections in developing countries such as Nepal. Aside from irrational practices of antibiotic use, mutations in chromosomal genes encoding DNA gyrase and Topoisomerase IV and by plasmid mediated quinolone resistant (PMQR) genes are suggested mechanisms for the development of resistance to nalidixic acid and reduced susceptibility to ciprofloxacin. Regardless of high endemicity of enteric fever in Nepal, there is paucity of studies on prevalence and drug-resistance of the pathogen. Read More

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