Structural signature of Ser83Leu and Asp87Asn mutations in DNA gyrase from enterotoxigenic Escherichia coli and impact on quinolone resistance

Mehla, Kusum; Ramana, Jayashree

doi:10.1016/j.gene.2015.09.063

Cited by 13 publications

(10 citation statements)

References 30 publications

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“…Moreover, the binding energy was negatively correlated with their MICs (Figure and Table S4). These results agree with a previous finding where the Ser83Leu substitution in gyr A remarkably affected ciprofloxacin binding, causing a relatively low docking score . Furthermore, the binding energies between ciprofloxacin and normal/mutated GyrA were −15.271, −12.327, and −9.126 kcal/mol for wild-type GyrA, mutated EM100d GyrA, and mutated CM100d GyrA, respectively.…”

Section: Resultssupporting

confidence: 91%

“…The most common mechanism for fluoroquinolone resistance developed under high concentrations of this antibiotic is due to one or more substitutions in the quinolone resistance-determining region of the target genes (e.g., gyrA, gyrB, parC, and parE). 67 Mutants that shared the same mutations showed different levels of resistance, suggesting that additional resistance mechanisms (efflux pump and porin downregulation) can contribute to the resistance phenotype. 54 In this study, both fluoroquinolone-resistant mutants (EM100d and CM100d) shared the substitutions in gyrA and the downregulation of porin expression.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

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Fluoroquinolone Residues in the Environment Rapidly Induce Heritable Fluoroquinolone Resistance in Escherichia coli

Liang

Zhang

et al. 2023

Environ. Sci. Technol.

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Extensive antibiotic use increases the environmental presence of their residues and may accelerate the development of antibiotic resistance, although this remains poorly understood at environmentally relevant concentrations. Herein, susceptible Escherichia coli K12 was continuously exposed to five antibiotics at such concentrations for 100 days. The de novo-evolved mutants rapidly obtained fluoroquinolone resistance within 10 days, as indicated by the 4and 16-fold augmentation of minimum inhibitory concentrations against enrofloxacin and ciprofloxacin, respectively. Moreover, the mutants maintained heritable fluoroquinolone resistance after the withdrawal of antibiotics for 30 days. Genomic analysis identified Asp87Gly or Ser83Leu substitutions in the gyrA gene in the mutants. Transcriptomics data showed that the transcriptional response of the mutants to fluoroquinolones was primarily involved in biofilm formation, cellular motility, porin, oxidative stress defense, and energy metabolism. Homologous recombination and molecular docking revealed that mutations of gyrA primarily mainly conferred fluoroquinolone resistance, while mutations at different positions of gyrA likely endowed different fluoroquinolone resistance levels. Collectively, this study revealed that environmentally relevant concentrations of antibiotics could rapidly induce heritable antibiotic resistance; therefore, the discharge of antibiotics into the environment should be rigorously controlled to prevent the development of antibiotic resistance.

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Section: Resultssupporting

confidence: 91%

Section: ■ Materials and Methodsmentioning

confidence: 99%

Fluoroquinolone Residues in the Environment Rapidly Induce Heritable Fluoroquinolone Resistance in Escherichia coli

Liang

Zhang

et al. 2023

Environ. Sci. Technol.

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“…In the last decades, antibiotic resistances have been described in several microorganisms, including those having multiresistance phenotypes [1,2,3,4]. This is an alarming situation, as noted by the World Health Organization, and many researchers have focused on the development of new therapeutic alternatives.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Antimicrobial, Antioxidant, and Leishmanicidal Activities of Schiff Base Derivatives of 4-Aminoantipyrine

et al. 2019

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Our main interest is the characterization of compounds to support the development of alternatives to currently marketed drugs that are losing effectiveness due to the development of resistance. Schiff bases are promising biologically interesting compounds having a wide range of pharmaceutical properties, including anti-inflammatory, antipyretic, and antimicrobial activities, among others. In this work, we have synthesized 12 Schiff base derivatives of 4-aminoantipyrine. In vitro antimicrobial, antioxidant, and cytotoxicity properties are analyzed, as well as in silico predictive adsorption, distribution, metabolism, and excretion (ADME) and bioactivity scores. Results identify two potential Schiff bases: one effective against E. faecalis and the other with antioxidant activity. Both have reasonable ADME scores and provides a scaffold for developing more effective compounds in the future. Initial studies are usually limited to laboratory in vitro approaches, and following these initial studies, much research is needed before a drug can reach the clinic. Nevertheless, these laboratory approaches are mandatory and constitute a first filter to discriminate among potential drug candidates and chemical compounds that should be discarded.

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“…Firstly by modifying the target enzyme and second by limiting the permeability of the drug (Nikaido 1998;Hernandez et al 2011). In majority of the cases, there is an amino acid substitution in quinolone-resistancedetermining region, which introduces a bulky hydrophobic residue instead of a polar hydroxyl group (Mehla and Ramana 2016). DNA gyrase activity is mostly inhibited in gram-negative bacteria, but in gram-positive either DNA gyrase or topoisomerase IV can be inhibited depending on the choice of fluoroquinolones used (Jacoby 2005).…”

Section: Quinolone Resistancementioning

confidence: 99%

Drug Resistance in Bacteria, Fungi, Malaria, and Cancer

Godman

Fadare

Kibuule

et al. 2017

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Structural signature of Ser83Leu and Asp87Asn mutations in DNA gyrase from enterotoxigenic Escherichia coli and impact on quinolone resistance

Cited by 13 publications

References 30 publications

Fluoroquinolone Residues in the Environment Rapidly Induce Heritable Fluoroquinolone Resistance in Escherichia coli

Fluoroquinolone Residues in the Environment Rapidly Induce Heritable Fluoroquinolone Resistance in Escherichia coli

Characterization of Antimicrobial, Antioxidant, and Leishmanicidal Activities of Schiff Base Derivatives of 4-Aminoantipyrine

Drug Resistance in Bacteria, Fungi, Malaria, and Cancer

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