Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes

The widely used quinolone antibiotics act by trapping prokaryotic type IIA topoisomerases, resulting in irreversible topoisomerase cleavage complexes (TOPcc). Whereas the excision repair pathways of TOPcc in eukaryotes have been extensively studied, it is not known whether equivalent repair pathways for prokaryotic TOPcc exist. By combining genetic, biochemical, and molecular biology approaches, we demonstrate that exonuclease VII (ExoVII) excises quinolone-induced trapped DNA gyrase, an essential prokaryotic type IIA topoisomerase. We show that ExoVII repairs trapped type IIA TOPcc and that ExoVII displays tyrosyl nuclease activity for the tyrosyl-DNA linkage on the 5′-DNA overhangs corresponding to trapped type IIA TOPcc. ExoVII-deficient bacteria fail to remove trapped DNA gyrase, consistent with their hypersensitivity to quinolones. We also identify an ExoVII inhibitor that synergizes with the antimicrobial activity of quinolones, including in quinolone-resistant bacterial strains, further demonstrating the functional importance of ExoVII for the repair of type IIA TOPcc.

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Synthesis, Identification, Computer-Aided Docking Studies, and ADMET Prediction of Novel Benzimidazo-1,2,3-triazole Based Molecules as Potential Antimicrobial Agents

Molecules ◽

10.3390/molecules26237119 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7119

Author(s):

Huda R. M. Rashdan ◽

Aboubakr H. Abdelmonsef ◽

Mortaga M. Abou-Krisha ◽

Tarek A. Yousef

Keyword(s):

Antimicrobial Activity ◽

Binding Energy ◽

Antimicrobial Agents ◽

Sodium Ethoxide ◽

Dna Gyrase ◽

Docking Studies ◽

Bacterial Strains ◽

Standard Drug ◽

E Coli

2-azido-1H-benzo[d]imidazole derivatives 1a,b were reacted with a β-ketoester such as acetylacetone in the presence of sodium ethoxide to obtain the desired molecules 2a,b. The latter acted as a key molecule for the synthesis of new carbazone derivatives 4a,b that were submitted to react with 2-oxo-N-phenyl-2-(phenylamino)acetohydrazonoyl chloride to obtain the target thiadiazole derivatives 6a,b. The structures of the newly synthesized compounds were inferred from correct spectral and microanalytical data. Moreover, the newly prepared compounds were subjected to molecular docking studies with DNA gyrase B and exhibited binding energy that extended from −9.8 to −6.4 kcal/mol, which confirmed their excellent potency. The compounds 6a,b were found to be with the minimum binding energy (−9.7 and −9.8 kcal/mol) as compared to the standard drug ciprofloxacin (−7.4 kcal/mol) against the target enzyme DNA gyrase B. In addition, the newly synthesized compounds were also examined and screened for their in vitro antimicrobial activity against pathogenic microorganisms Staphylococcus aureus, E. coli, Pseudomonas aeruginosa, Aspergillus niger, and Candida albicans. Among the newly synthesized molecules, significant antimicrobial activity against all the tested microorganisms was obtained for the compounds 6a,b. The in silico and in vitro findings showed that compounds 6a,b were the most active against bacterial strains, and could serve as potential antimicrobial agents.

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In vitro antimicrobial activity of marbofloxacin and enrofloxacin against bacterial strains isolated from companion animals

Schweizer Archiv für Tierheilkunde ◽

10.1024/0036-7281.149.6.265 ◽

2007 ◽

Vol 149 (6) ◽

pp. 265-271 ◽

Cited By ~ 7

Author(s):

A. M. Farca ◽

P. Cavana ◽

P. Robino ◽

P. Nebbia

Keyword(s):

Antimicrobial Activity ◽

Companion Animals ◽

Bacterial Strains ◽

In Vitro Antimicrobial Activity

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SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF 3-FORMYL INDOLE BASED SCHIFF BASES

Journal of Biomedical and Pharmaceutical Research ◽

10.32553/jbpr.v7i6.561 ◽

2018 ◽

Vol 7 (6) ◽

Author(s):

Singh Gurvinder ◽

Singh Prabhsimran ◽

Dhawan R. K.

Keyword(s):

Antimicrobial Activity ◽

Spectral Analysis ◽

Schiff Bases ◽

Antimicrobial Agents ◽

Biological Evaluation ◽

Fungal Strain ◽

Bacterial Strains ◽

Standard Drug ◽

Gram Negative ◽

E Coli

In order to develop new antimicrobial agents, a series of 3-formyl indole based Schiff bases were synthesized by reacting 3-formyl indole(indole-3-carboxaldehyde) with substituted aniline taking ethanol as solvent. The reaction was carried in the presence of small amount of p-toluene sulphonic acid as catalyst.All the synthesized compounds were characterized by IR, 1H-NMR spectral analysis. All the synthesized compounds were evaluated for antimicrobial activity against two gram positive bacterial strains (B. subtilisand S. aureus) and two gram negative bacterial strains (P. aeruginosaand E. coli) and one fungal strain (C. albicans). All the synthesized compounds were found to have moderate to good antimicrobial activity. The standard drug amoxicillin, fluconazole were used for antimicrobial activity. Among the synthesized compounds, the maximum antimicrobial activity was shown by compounds GS04, GS07, GS08 and GS10.

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Antimicrobial Activity of Iron-Halide Complexes Against Gram-Positive and Gram-Negative Bacteria

10.26434/chemrxiv.11864934.v1 ◽

2020 ◽

Author(s):

Nusrat Abedin ◽

Abdullah Hamed A Alshehri ◽

Ali M A Almughrbi ◽

Olivia Moore ◽

Sheikh Alyza ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antimicrobial Resistance ◽

Extracellular Dna ◽

Antibiofilm Activity ◽

Gram Negative Bacteria ◽

Bacterial Strains ◽

Gram Positive ◽

Gram Negative ◽

Antimicrobial Substances ◽

Mammalian Cell Lines

Antimicrobial resistance (AMR) has become one of the more serious threats to the global health. The emergence of bacteria resistant to antimicrobial substances decreases the potencies of current antibiotics. Consequently, there is an urgent and growing need for the developing of new classes of antibiotics. Three prepared novel iron complexes have a broad-spectrum antimicrobial activity with minimum bactericidal concentration (MBC) values ranging from 3.5 to 10 mM and 3.5 to 40 mM against Gram-positive and Gram-negative bacteria with antimicrobial resistance phenotype, respectively. Time-kill studies and quantification of the extracellular DNA confirmed the bacteriolytic mode of action of the iron-halide compounds. Additionally, the novel complexes showed significant antibiofilm activity against the tested pathogenic bacterial strains at concentrations lower than the MBC. The cytotoxic effect of the complexes on different mammalian cell lines show sub-cytotoxic values at concentrations lower than the minimum bactericidal concentrations.

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Fabrication and Characterization of Antimicrobial Magnetron Cosputtered TiO2/Ag/Cu Composite Coatings

Coatings ◽

10.3390/coatings11040473 ◽

2021 ◽

Vol 11 (4) ◽

pp. 473

Author(s):

Dilyana Gospodonova ◽

Iliana Ivanova ◽

Todorka Vladkova

Keyword(s):

Antimicrobial Activity ◽

Composite Coatings ◽

Surface Characteristics ◽

Standard Test ◽

Most Probable Number ◽

Bacterial Strains ◽

Probable Number ◽

Fabrication And Characterization

The aim of this study was to prepare TiO2/Ag/Cu magnetron co-sputtered coatings with controlled characteristics and to correlate them with the antimicrobial activity of the coated glass samples. The elemental composition and distribution, surface morphology, wettability, surface energy and its component were estimated as the surface characteristics influencing the bioadhesion. Well expressed, specific, Ag/Cu concentration-dependent antimicrobial activity in vitro was demonstrated toward Gram-negative and Gram-positive standard test bacterial strains both by diffusion 21 assay and by Most Probable Number of surviving cells. Direct contact and eluted silver/coper nanoparticles killing were experimentally demonstrated as a mode of the antimicrobial action of the studied TiO2/Ag/Cu thin composite coatings. It is expected that they would ensure a broad spectrum bactericidal activity during the indwelling of the coated medical devices and for at least 12 h after that, with the supposition that the benefits will be over a longer time.

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Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways

International Journal of Molecular Sciences ◽

10.3390/ijms22052698 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2698

Author(s):

Vladimir Shafirovich ◽

Nicholas E. Geacintov

Keyword(s):

Excision Repair ◽

Dna Lesions ◽

Dna Templates ◽

Circular Dna ◽

Damage Sensing ◽

Cell Extracts ◽

Dna Base ◽

Nucleotide Excision ◽

Repair Pathways ◽

Cellular Dna

The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.

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Sulfaguanidine Hybrid with Some New Pyridine-2-One Derivatives: Design, Synthesis, and Antimicrobial Activity against Multidrug-Resistant Bacteria as Dual DNA Gyrase and DHFR Inhibitors

Antibiotics ◽

10.3390/antibiotics10020162 ◽

2021 ◽

Vol 10 (2) ◽

pp. 162

Author(s):

Ahmed Ragab ◽

Sawsan A. Fouad ◽

Ola A. Abu Ali ◽

Entsar M. Ahmed ◽

Abeer M. Ali ◽

...

Keyword(s):

Antimicrobial Activity ◽

Fungal Growth ◽

Dna Gyrase ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Design Synthesis ◽

Potent Inhibition ◽

Ic50 Values ◽

Dhfr Inhibitors ◽

Positive Controls

Herein, a series of novel hybrid sulfaguanidine moieties, bearing 2-cyanoacrylamide 2a–d, pyridine-2-one 3–10, and 2-imino-2H-chromene-3-carboxamide 11, 12 derivatives, were synthesized, and their structure confirmed by spectral data and elemental analysis. All the synthesized compounds showed moderate to good antimicrobial activity against eight pathogens. The most promising six derivatives, 2a, 2b, 2d, 3a, 8, and 11, revealed to be best in inhibiting bacterial and fungal growth, thus showing bactericidal and fungicidal activity. These derivatives exhibited moderate to potent inhibition against DNA gyrase and DHFR enzymes, with three derivatives 2d, 3a, and 2a demonstrating inhibition of DNA gyrase, with IC50 values of 18.17–23.87 µM, and of DHFR, with IC50 values of 4.33–5.54 µM; their potency is near to that of the positive controls. Further, the six derivatives exhibited immunomodulatory potential and three derivatives, 2d, 8, and 11, were selected for further study and displayed an increase in spleen and thymus weight and enhanced the activation of CD4+ and CD8+ T lymphocytes. Finally, molecular docking and some AMED studies were performed.

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Characterization and Antibacterial Response of Silver Nanoparticles Biosynthesized Using an Ethanolic Extract of Coccinia indica Leaves

Crystals ◽

10.3390/cryst11020097 ◽

2021 ◽

Vol 11 (2) ◽

pp. 97

Author(s):

Suresh V. Chinni ◽

Subash C. B. Gopinath ◽

Periasamy Anbu ◽

Neeraj Kumar Fuloria ◽

Shivkanya Fuloria ◽

...

Keyword(s):

Electron Microscopy ◽

Antimicrobial Activity ◽

Silver Nanoparticles ◽

Zeta Potential ◽

Ethanolic Extract ◽

Spherical Shape ◽

Bacterial Strains ◽

X Ray ◽

Coccinia Indica ◽

Antibacterial Potential

The present study was planned to characterize and analyze the antimicrobial activity of silver nanoparticles (AgNP) biosynthesized using a Coccinia indica leaf (CIL) ethanolic extract. The present study included the preparation of CIL ethanolic extract using the maceration process, which was further used for AgNP biosynthesis by silver nitrate reduction. Biosynthetic AgNPs were characterized using UV–Visible spectrometry, zeta potential analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray diffraction (XRD), and energy-dispersive X-ray (EDX) spectrometry. The biogenic AgNP and CIL extracts were further investigated against different bacterial strains for their antimicrobial activity. The surface plasmon resonance (SPR) signal at 425 nm confirmed AgNP formation. The SEM and TEM data revealed the spherical shape of biogenic AgNPs and size in the range of 8 to 48 nm. The EDX results verified the presence of Ag. The AgNPs displayed a zeta potential of −55.46 mV, suggesting mild AgNP stability. Compared to Gram-positive bacteria, the biogenic AgNPs demonstrated high antibacterial potential against Gram-negative bacteria. Based on the results, the current study concluded that AgNPs based on CIL extract have strong antibacterial potential, and it established that AgNP biosynthesis using CIL ethanol extract is an effective process.

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Antimicrobial Activity of Cyclic-Monomeric and Dimeric Derivatives of the Snail-Derived Peptide Cm-p5 against Viral and Multidrug-Resistant Bacterial Strains

Biomolecules ◽

10.3390/biom11050745 ◽

2021 ◽

Vol 11 (5) ◽

pp. 745

Author(s):

Melaine González-García ◽

Fidel Morales-Vicente ◽

Erbio Díaz Pico ◽

Hilda Garay ◽

Daniel G. Rivera ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Antimicrobial Activity ◽

Antifungal Activity ◽

Multidrug Resistant ◽

Moderate Activity ◽

Dependent Manner ◽

Bacterial Strains ◽

Acinetobacter Baumanii ◽

Concentration Dependent Manner ◽

Conventional Antibiotics

Cm-p5 is a snail-derived antimicrobial peptide, which demonstrated antifungal activity against the pathogenic strains of Candida albicans. Previously we synthetized a cyclic monomer as well as a parallel and an antiparallel dimer of Cm-p5 with improved antifungal activity. Considering the alarming increase of microbial resistance to conventional antibiotics, here we evaluated the antimicrobial activity of these derivatives against multiresistant and problematic bacteria and against important viral agents. The three peptides showed a moderate activity against Pseudomonas aeruginosa, Klebsiella pneumoniae Extended Spectrum β-Lactamase (ESBL), and Streptococcus agalactiae, with MIC values > 100 µg/mL. They exerted a considerable activity with MIC values between 25–50 µg/mL against Acinetobacter baumanii and Enterococcus faecium. In addition, the two dimers showed a moderate activity against Pseudomonas aeruginosa PA14. The three Cm-p5 derivatives inhibited a virulent extracellular strain of Mycobacterium tuberculosis, in a dose-dependent manner. Moreover, they inhibited Herpes Simplex Virus 2 (HSV-2) infection in a concentration-dependent manner, but had no effect on infection by the Zika Virus (ZIKV) or pseudoparticles of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2). At concentrations of >100 µg/mL, the three new Cm-p5 derivatives showed toxicity on different eukaryotic cells tested. Considering a certain cell toxicity but a potential interesting activity against the multiresistant strains of bacteria and HSV-2, our compounds require future structural optimization.

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