scholarly journals Nybomycin Inhibits both Fluoroquinolone-Sensitive and Fluoroquinolone-Resistant Escherichia coli DNA Gyrase

2021 ◽  
Vol 65 (5) ◽  
Author(s):  
Dmitrii I. Shiriaev ◽  
Alina A. Sofronova ◽  
Ekaterina A. Berdnikovich ◽  
Dmitrii A. Lukianov ◽  
Ekaterina S. Komarova ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Bacterial Species ◽  
Dna Gyrase ◽  
Resistant Bacteria ◽  
Mutant Form ◽  
Wild Type ◽  
Topoisomerase Iv ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type

ABSTRACT Bacterial type II topoisomerases, DNA gyrase and topoisomerase IV, are targets of many antibiotics, including fluoroquinolones (FQs). Unfortunately, a number of bacterial species easily acquire resistance to FQs by mutations in either DNA gyrase or topoisomerase IV genes. The emergence of resistant pathogenic strains is a global problem in health care; therefore, identifying alternative pathways to thwart their persistence is the current frontier in drug discovery. Nybomycins are an attractive class of compounds, reported to be “reverse antibiotics” that selectively inhibit growth of some Gram-positive FQ-resistant bacteria by targeting the mutant form of DNA gyrase while being inactive against wild-type strains with FQ-sensitive gyrases. The strong “reverse” effect was demonstrated only for a few Gram-positive organisms resistant to FQs due to the S83L/I mutation in the GyrA subunit of DNA gyrase. However, the activity of nybomycins has not been extensively explored among Gram-negative species. Here, we observed that in a ΔtolC strain of the Gram-negative Escherichia coli with enhanced permeability, wild-type gyrase and a GyrA S83L mutant, resistant to fluoroquinolones, are similarly sensitive to nybomycin.

scholarly journals In VitroActivity of AZD0914, a Novel Bacterial DNA Gyrase/Topoisomerase IV Inhibitor, against Clinically Relevant Gram-Positive and Fastidious Gram-Negative Pathogens

2015 ◽  
Vol 59 (10) ◽  
pp. 6053-6063 ◽  
Author(s):  
Douglas J. Biedenbach ◽  
Michael D. Huband ◽  
Meredith Hackel ◽  
Boudewijn L. M. de Jonge ◽  
Daniel F. Sahm ◽  
...  
Keyword(s):  
Bacterial Species ◽  
Dna Gyrase ◽  
Species Group ◽  
Coagulase Negative Staphylococci ◽  
Topoisomerase Iv ◽  
Gram Positive ◽  
Bacterial Dna ◽  
Gram Negative ◽  
Content Type

ABSTRACTAZD0914, a new spiropyrimidinetrione bacterial DNA gyrase inhibitor with a novel mode of inhibition, has activity against bacterial species commonly cultured from patient infection specimens, including fluoroquinolone-resistant isolates. This study assessed thein vitroactivity of AZD0914 against key Gram-positive and fastidious Gram-negative clinical isolates collected globally in 2013. AZD0914 demonstrated potent activity, with MIC90s for AZD0914 of 0.25 mg/liter againstStaphylococcus aureus(n= 11,680), coagulase-negative staphylococci (n= 1,923), streptococci (n= 4,380), andMoraxella catarrhalis(n= 145), 0.5 mg/liter againstStaphylococcus lugdunensis(n= 120) andHaemophilus influenzae(n= 352), 1 mg/liter againstEnterococcus faecalis(n= 1,241), and 2 mg/liter againstHaemophilus parainfluenzae(n= 70). The activity againstEnterococcus faeciumwas more limited (MIC90, 8 mg/liter). The spectrum and potency of AZD0914 included fluoroquinolone-resistant isolates in each species group, including methicillin-resistant staphylococci, penicillin-resistant streptococci, vancomycin-resistant enterococci, β-lactamase-producingHaemophilusspp., andM. catarrhalis. Based on thesein vitrofindings, AZD0914 warrants further investigation for its utility against a variety of Gram-positive and fastidious Gram-negative bacterial species.

scholarly journals In VitroAntibacterial Activity of AZD0914, a New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-Positive, Fastidious Gram-Negative, and Atypical Bacteria

2014 ◽  
Vol 59 (1) ◽  
pp. 467-474 ◽  
Author(s):  
Michael D. Huband ◽  
Patricia A. Bradford ◽  
Linda G. Otterson ◽  
Gregory S. Basarab ◽  
Amy C. Kutschke ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Legionella Pneumophila ◽  
Bacterial Species ◽  
Dna Gyrase ◽  
Cross Resistance ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Topoisomerase Inhibitor

ABSTRACTAZD0914 is a new spiropyrimidinetrione bacterial DNA gyrase/topoisomerase inhibitor with potentin vitroantibacterial activity against key Gram-positive (Staphylococcus aureus,Staphylococcus epidermidis,Streptococcus pneumoniae,Streptococcus pyogenes, andStreptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzaeandNeisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with known resistance to fluoroquinolones. AZD0914 works via inhibition of DNA biosynthesis and accumulation of double-strand cleavages; this mechanism of inhibition differs from those of other marketed antibacterial compounds. AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA under permissive conditions and thus blocks religation of the double-strand cleaved DNA to form fused circular DNA. Whereas this mechanism is similar to that seen with fluoroquinolones, it is mechanistically distinct. AZD0914 exhibited low frequencies of spontaneous resistance inS. aureus, and if mutants were obtained, the mutations mapped togyrB. Additionally, no cross-resistance was observed for AZD0914 against recent bacterial clinical isolates demonstrating resistance to fluoroquinolones or other drug classes, including macrolides, β-lactams, glycopeptides, and oxazolidinones. AZD0914 was bactericidal in both minimum bactericidal concentration andin vitrotime-kill studies. Inin vitrocheckerboard/synergy testing with 17 comparator antibacterials, only additivity/indifference was observed. The potentin vitroantibacterial activity (including activity against fluoroquinolone-resistant isolates), low frequency of resistance, lack of cross-resistance, and bactericidal activity of AZD0914 support its continued development.

scholarly journals Inhibition of Neisseria gonorrhoeae Type II Topoisomerases by the Novel Spiropyrimidinetrione AZD0914

2015 ◽  
Vol 290 (34) ◽  
pp. 20984-20994 ◽  
Author(s):  
Gunther Kern ◽  
Tiffany Palmer ◽  
David E. Ehmann ◽  
Adam B. Shapiro ◽  
Beth Andrews ◽  
...  
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Bacterial Species ◽  
Dna Gyrase ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Type Ii ◽  
Topoisomerase Iv ◽  
Gram Positive ◽  
Gram Negative

We characterized the inhibition of Neisseria gonorrhoeae type II topoisomerases gyrase and topoisomerase IV by AZD0914 (AZD0914 will be henceforth known as ETX0914 (Entasis Therapeutics)), a novel spiropyrimidinetrione antibacterial compound that is currently in clinical trials for treatment of drug-resistant gonorrhea. AZD0914 has potent bactericidal activity against N. gonorrhoeae, including multidrug-resistant strains and key Gram-positive, fastidious Gram-negative, atypical, and anaerobic bacterial species (Huband, M. D., Bradford, P. A., Otterson, L. G., Basrab, G. S., Giacobe, R. A., Patey, S. A., Kutschke, A. C., Johnstone, M. R., Potter, M. E., Miller, P. F., and Mueller, J. P. (2014) In Vitro Antibacterial Activity of AZD0914: A New Spiropyrimidinetrione DNA Gyrase/Topoisomerase Inhibitor with Potent Activity against Gram-positive, Fastidious Gram-negative, and Atypical Bacteria. Antimicrob. Agents Chemother. 59, 467–474). AZD0914 inhibited DNA biosynthesis preferentially to other macromolecules in Escherichia coli and induced the SOS response to DNA damage in E. coli. AZD0914 stabilized the enzyme-DNA cleaved complex for N. gonorrhoeae gyrase and topoisomerase IV. The potency of AZD0914 for inhibition of supercoiling and the stabilization of cleaved complex by N. gonorrhoeae gyrase increased in a fluoroquinolone-resistant mutant enzyme. When a mutation, conferring mild resistance to AZD0914, was present in the fluoroquinolone-resistant mutant, the potency of ciprofloxacin for inhibition of supercoiling and stabilization of cleaved complex was increased greater than 20-fold. In contrast to ciprofloxacin, religation of the cleaved DNA did not occur in the presence of AZD0914 upon removal of magnesium from the DNA-gyrase-inhibitor complex. AZD0914 had relatively low potency for inhibition of human type II topoisomerases α and β.

scholarly journals Development of Methionyl-tRNA Synthetase Inhibitors as Antibiotics for Gram-Positive Bacterial Infections

2017 ◽  
Vol 61 (11) ◽  
Author(s):  
Omeed Faghih ◽  
Zhongsheng Zhang ◽  
Ranae M. Ranade ◽  
J. Robert Gillespie ◽  
Sharon A. Creason ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Bacterial Species ◽  
Bacterial Load ◽  
Trna Synthetase ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Methionyl Trna Synthetase

ABSTRACT Antibiotic-resistant bacteria are widespread and pose a growing threat to human health. New antibiotics acting by novel mechanisms of action are needed to address this challenge. The bacterial methionyl-tRNA synthetase (MetRS) enzyme is essential for protein synthesis, and the type found in Gram-positive bacteria is substantially different from its counterpart found in the mammalian cytoplasm. Both previously published and new selective inhibitors were shown to be highly active against Gram-positive bacteria with MICs of ≤1.3 μg/ml against Staphylococcus, Enterococcus, and Streptococcus strains. Incorporation of radioactive precursors demonstrated that the mechanism of activity was due to the inhibition of protein synthesis. Little activity against Gram-negative bacteria was observed, consistent with the fact that Gram-negative bacterial species contain a different type of MetRS enzyme. The ratio of the MIC to the minimum bactericidal concentration (MBC) was consistent with a bacteriostatic mechanism. The level of protein binding of the compounds was high (>95%), and this translated to a substantial increase in MICs when the compounds were tested in the presence of serum. Despite this, the compounds were very active when they were tested in a Staphylococcus aureus murine thigh infection model. Compounds 1717 and 2144, given by oral gavage, resulted in 3- to 4-log decreases in the bacterial load compared to that in vehicle-treated mice, which was comparable to the results observed with the comparator drugs, vancomycin and linezolid. In summary, the research describes MetRS inhibitors with oral bioavailability that represent a class of compounds acting by a novel mechanism with excellent potential for clinical development.

Microbiological pattern of prosthetic hip and knee infections: a high-volume, single-centre experience in China

2021 ◽  
Author(s):  
Yali Yu ◽  
Yiyi Kong ◽  
Jing Ye ◽  
Aiguo Wang ◽  
Wenteng Si
Keyword(s):  
Antibiotic Treatment ◽  
Prolonged Treatment ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Musculoskeletal Infection ◽  
Gram Negative ◽  
Content Type ◽  
Empirical Antibiotic Treatment ◽  
Link Type

Introduction. Prosthetic joint infection (PJI) is a serious complication after arthroplasty, which results in high morbidity, prolonged treatment and considerable healthcare expenses in the absence of accurate diagnosis. In China, microbiological data on PJIs are still scarce. Hypothesis/Gap Statement. The incidence of PJI is increasing year by year, and the proportion of drug-resistant bacteria infection is nicreasing, which brings severe challenges to the treatment of infection. Aim. This study aimed to identify the pathogens in PJIs, multi-drug resistance, and evaluate the effect of the treatment regimen in patients with PJI. Methodology. A total of 366 consecutive cases of PJI in the hip or knee joint were admitted at the Orthopedic Surgery Center in Zhengzhou, China from January 2012 to December 2018. Infections were confirmed in accordance with the Infectious Diseases Society of America and the Musculoskeletal Infection Society (MSIS) criteria. Concurrently, patient demographic data, incidence and antibiotic resistance were investigated. Statistical differences were analysed using Fisher’s exact test or chi-square test. Results. Altogether, 318 PJI cases satisfying the inclusion criteria were enrolled in this study, including 148 with hip PJIs and 170 with knee PJIs. The average age of patients with hip PJIs was lesser than that of patients with knee PJIs (56.4 vs. 68.6 years). Meanwhile, coagulase-negative staphylococcus (CNS, n=81, 25.5 %) was the predominant causative pathogen, followed by Staphylococcus aureus (n=67, 21.1 %). Methicillin-resistant Staphylococcus (MRS) was identified in 28.9 % of PJI patients. In addition, fungus accounted for 4.8 % (n=15), non-tuberculosis mycobacterium accounted for 1.6 % (n=5), polymicrobial pathogens accounted for 21.7 % (n=69), and Gram-negative bacteria accounted for 7.9 % (n=25) of the total infections. The results of antibiotic susceptibility testing showed that gentamicin and clindamycin β-lactam antibiotics were poorly susceptible to Gram-positive isolates, but they were sensitive to rifampicin, linezolid and vancomycin. While antibiotics such as amikacin and imipenem were effective against Gram-negative bacteria, there was a high resistance rate of other pathogens to gentamicin, clindamycin and some quinolone antibacterial drugs. Empirical antibiotic treatment should combine vancomycin and cephalosporin, levofloxacin or clindamycin. When the pathogen is confirmed, the treatment should be individualized. Conclusions. The prevalence of culture-negative PJIs is still very high. Gram-positive bacteria are still the main type of pathogens that cause PJIs. Attention should be paid to the high incidence of MRS, such as MRSA and MR-CNS, among PJI patients. Empirical antibiotic treatment should cover Gram-positive isolates, especially Staphylococcus .

scholarly journals Identification and Characterization of the First Cholesterol-Dependent Cytolysins from Gram-Negative Bacteria

2012 ◽  
Vol 81 (1) ◽  
pp. 216-225 ◽  
Author(s):  
Eileen M. Hotze ◽  
Huynh M. Le ◽  
Jessica R. Sieber ◽  
Christina Bruxvoort ◽  
Michael J. McInerney ◽  
...  
Keyword(s):  
Cell Structure ◽  
Bacterial Species ◽  
Cytolytic Activity ◽  
Opportunistic Pathogens ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Positive Type ◽  
Secretion Signal ◽  
Anaerobic Soils

The cholesterol-dependent cytolysins (CDCs) are pore-forming toxins that have been exclusively associated with a wide variety of bacterial pathogens and opportunistic pathogens from theFirmicutesandActinobacteria, which exhibit a Gram-positive type of cell structure. We have characterized the first CDCs from Gram-negative bacterial species, which includeDesulfobulbus propionicustype species Widdel 1981 (DSM 2032) (desulfolysin [DLY]) andEnterobacter lignolyticus(formerlyEnterobacter cloacae) SCF1 (enterolysin [ELY]). The DLY and ELY primary structures show that they maintain the signature motifs of the CDCs but lack an obvious secretion signal. Recombinant, purified DLY (rDLY) and ELY (rELY) exhibited cholesterol-dependent binding and cytolytic activity and formed the typical large CDC membrane oligomeric pore complex. Unlike the CDCs from Gram-positive species, which are human- and animal-opportunistic pathogens, neitherD. propionicusnorE. lignolyticusis known to be a pathogen or commensal of humans or animals: the habitats of both organisms appear to be restricted to anaerobic soils and/or sediments. These studies reveal for the first time that the genes for functional CDCs are present in bacterial species that exhibit a Gram-negative cell structure. These are also the first bacterial species containing a CDC gene that are not known to inhabit or cause disease in humans or animals, which suggests a role of these CDCs in the defense against eukaryote bacterial predators.

scholarly journals Metabolic Engineering for l-Glutamine Overproduction by Using DNA Gyrase Mutations in Escherichia coli

2013 ◽  
Vol 79 (9) ◽  
pp. 3033-3039 ◽  
Author(s):  
Mikiro Hayashi ◽  
Kazuhiko Tabata
Keyword(s):  
Escherichia Coli ◽  
Metabolic Engineering ◽  
Topoisomerase I ◽  
Dna Gyrase ◽  
Chromosomal Dna ◽  
Topoisomerase Iv ◽  
Α Subunit ◽  
Content Type ◽  
Genome Wide ◽  
K 12

ABSTRACTAnl-glutamine-overproducing mutant of anEscherichia coliK-12-derived strain was selected from randomly mutagenized cells in the course ofl-alanyl-l-glutamine strain development. Genome-wide mutation analysis unveiled a novel mechanism forl-glutamine overproduction in this mutant. Three mutations were identified that are related to thel-glutamine overproduction phenotype, namely, an intergenic mutation in the 5′-flanking region ofyeiGand two nonsynonymous mutations ingyrA(Gly821Ser and Asp830Asn). Expression ofyeiG, which encodes a putative esterase, was enhanced by the intergenic mutation. The nonsynonymous mutations ingyrA, a gene that encodes the DNA gyrase α subunit, affected the DNA topology of the cells. Gyrase is a type II topoisomerase that adds negative supercoils to double-stranded DNA. When the opposing DNA-relaxing activity was enhanced by overexpressing topoisomerase I (topA) and topoisomerase IV (parCandparE), an increase inl-glutamine production was observed. These results indicate that a reduction of chromosomal DNA supercoils in the mutant caused an increase inl-glutamine accumulation. The mechanism underlying this finding is discussed in this paper. We also constructed anl-glutamine-hyperproducing strain by attenuating cellularl-glutamine degradation activity. Although the reconstituted mutant (withyeiGtogether withgyrA) produced 200 mMl-glutamine, metabolic engineering finally enabled construction of a mutant that accumulated more than 500 mMl-glutamine.

scholarly journals Molecular Characterization of Zinc (Zn) Resistant Bacteria in Banger River, Pekalongan, Indonesia

2018 ◽  
Vol 10 (3) ◽  
pp. 622-628
Author(s):  
Fitri Arum Sasi ◽  
Hermin Pancasakti Kusumaningrum ◽  
Anto Budiharjo
Keyword(s):  
Bacterial Species ◽  
Selective Medium ◽  
Resistant Bacteria ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Indigenous Bacteria ◽  
Gram Positive Bacteria ◽  
Sequences Analysis

Indigenous bacteria are able to remove the metals contamination in environment. This study aimed to assess the resistance of bacterial species to Zinc (Zn) in Banger River, Pekalongan City. The bacteria from three different parts of Banger River were isolated and inoculated in Zn-selective medium. Then, molecular identification to determine the bacteria species was conducted using polymerase chain reaction (PCR) by applying forward-reverse 16SrRNA gene primers. The sequences analysis was conducted using MUSCLE and MEGA6. There were seven dominant species that possibly resistant to Zn. Approximately, every isolate could reach more than 95 % from 2000 ppm of Zn in the medium. The higher absorption of Zn was found in Z5 isolate. The seven bacteria species were clustered into nine genera i.e. Klebsiela, Xenorhabdus, Cronobacter, Enterobacter, Escherichia, Shigella and Sporomusa known as Gram Negative bacteria and Clostridium and Bacillus as Gram Positive bacteria. In Gram Positive bacteria, especially Bacillus sp, carboxyl group in peptidoglycan play a role as metal binder. In Gram-negative bacteria, lipopolysaccharide (LPS) which is highly anionic component on the outer membrane, able to catch the Zn. Besides that, Enterobacter activates endogen antioxidants such as glutathione peroxidase (GSHPx), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD). The research found there was possible seven novel indigenous bacteria species in Banger that able to remove Zn from the sediment extremely. This finding can be developed as an eco-friendly approach to reduce metals pollution using local microorganisms.

scholarly journals Tumble Suppression Is a Conserved Feature of Swarming Motility

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Jonathan D. Partridge ◽  
Nguyen T. Q. Nhu ◽  
Yann S. Dufour ◽  
Rasika M. Harshey
Keyword(s):  
Escherichia Coli ◽  
Bacterial Species ◽  
Behavioral Adaptation ◽  
Diverse Group ◽  
Swarming Motility ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Surfactant Secretion ◽  
Motility Parameters

ABSTRACT Many bacteria use flagellum-driven motility to swarm or move collectively over a surface terrain. Bacterial adaptations for swarming can include cell elongation, hyperflagellation, recruitment of special stator proteins, and surfactant secretion, among others. We recently demonstrated another swarming adaptation in Escherichia coli, wherein the chemotaxis pathway is remodeled to decrease tumble bias (increase run durations), with running speeds increased as well. We show here that the modification of motility parameters during swarming is not unique to E. coli but is shared by a diverse group of bacteria we examined—Proteus mirabilis, Serratia marcescens, Salmonella enterica, Bacillus subtilis, and Pseudomonas aeruginosa—suggesting that increasing run durations and speeds are a cornerstone of swarming. IMPORTANCE Bacteria within a swarm move characteristically in packs, displaying an intricate swirling motion in which hundreds of dynamic rafts continuously form and dissociate as the swarm colonizes an increasing expanse of territory. The demonstrated property of E. coli to reduce its tumble bias and hence increase its run duration during swarming is expected to maintain and promote side-by-side alignment and cohesion within the bacterial packs. In this study, we observed a similar low tumble bias in five different bacterial species, both Gram positive and Gram negative, each inhabiting a unique habitat and posing unique problems to our health. The unanimous display of an altered run-tumble bias in swarms of all species examined in this investigation suggests that this behavioral adaptation is crucial for swarming.

scholarly journals Synthesis and Biological Evaluation of New Pyridothienopyrimidine Derivatives as Antibacterial Agents and Escherichia coli Topoisomerase II Inhibitors

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 695
Author(s):  
Eman M. Mohi El-Deen ◽  
Eman A. Abd El-Meguid ◽  
Eman A. Karam ◽  
Eman S. Nossier ◽  
Marwa F. Ahmed
Keyword(s):  
Escherichia Coli ◽  
Antibacterial Activity ◽  
Topoisomerase Ii ◽  
Antibacterial Agents ◽  
Dna Gyrase ◽  
Structural Features ◽  
Biological Evaluation ◽  
Topoisomerase Iv ◽  
Gram Negative

The growing resistance of bacteria to many antibiotics that have been in use for several decades has generated the need to discover new antibacterial agents with structural features qualifying them to overcome the resistance mechanisms. Thus, novel pyridothienopyrimidine derivatives (2a,b–a,b) were synthesized by a series of various reactions, starting with 3-aminothieno[2,3-b]pyridine-2-carboxamides (1a,b). Condensation of compounds 1a,b with cyclohexanone gave 1’H-spiro[cyclohexane-1,2’-pyrido[3’,2’:4,5]thieno[3,2-d]pyrimidin]-4’(3’H)-ones (2a,b), which in turn were utilized to afford the target 4-substituted derivatives (3a,b–8a,b). In vitro antibacterial activity evaluations of all the new compounds (2a,b–8a,b) were performed against six strains of Gram-negative and Gram-positive bacteria. The target compounds showed significant antibacterial activity, especially against Gram-negative strains. Moreover, the compounds (2a,b; 3a,b; 4a,b; and 5a,b) that exhibited potent activity against Escherichia coli were selected to screen their inhibitory activity against Escherichia coli topoisomerase II (DNA gyrase and topoisomerase IV) enzymes. Compounds 4a and 4b showed potent dual inhibition of the two enzymes with IC50 values of 3.44 µΜ and 5.77 µΜ against DNA gyrase and 14.46 µΜ and 14.89 µΜ against topoisomerase IV, respectively. In addition, docking studies were carried out to give insight into the binding mode of the tested compounds within the E. coli DNA gyrase B active site compared with novobiocin.

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