Dioxidine induces bacterial resistance to antibiotics

Mazanko, Maria S.; Chistyakov, V. A.; Празднова, Е. В.; Pokudina, I. O.; Churilov, M. N.; Chmyhalo, V. K.; Батюшин, М. М.

doi:10.3103/s0891416816040066

Cited by 6 publications

(5 citation statements)

References 6 publications

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“…As it has been previously shown, that DIOX induces SOS-response in bacterial cells [37], the mechanism of antibacterial activity of novel 3-trifluoromethylquinoxaline 1,4-dioxides was analyzed by means of the pDualrep2 reported system [38]. In this reporter expression, turboRFP gene is under regulation of sulA promoter and upregulated in the presence of SOS-response inducers (topoisomerase inhibitors, DNA-intercalators etc), while The obtained results, presented in Figure 3, show that most of the new derivatives of 3-trifluoromethylquinoxaline 1,4-dioxide 12-15 as well as reference drug DIOX strongly caused DNA damage and induced SOS response in E. coli BW25513 strain, which corresponded with previous report of a DNA damaging mode of action of quinoxaline 1,4dioxides induced by oxidative stress in pathogens [39].…”

Section: Mechanism Of Action Determinationmentioning

confidence: 65%

“…As it has been previously shown, that DIOX induces SOS-response in bacterial cells [37], the mechanism of antibacterial activity of novel 3-trifluoromethylquinoxaline 1,4-dioxides was analyzed by means of the pDualrep2 reported system [38]. In this reporter expression, turboRFP gene is under regulation of sulA promoter and upregulated in the presence of SOS-response inducers (topoisomerase inhibitors, DNA-intercalators etc), while Katu-shka2S is expressed in the presence of translation inhibitors, due to the stalling of the ribosomes at the modified TrpL leader peptide which leads to transcription antitermination.…”

Section: Mechanism Of Action Determinationmentioning

confidence: 65%

“…Reporter strain E. coli BW25113 -pDualrep2 was used as previously described [37]. A total of 1 µL of 20 mg/mL solution of each sample was applied to agar plate containing a lawn of the reporter strain.…”

Section: Mechanism Of Action Determinationmentioning

confidence: 99%

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Synthesis and Characterization of Novel 2-Acyl-3-trifluoromethylquinoxaline 1,4-Dioxides as Potential Antimicrobial Agents

et al. 2022

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The emergence of drug resistance in pathogens leads to a loss of effectiveness of antimicrobials and complicates the treatment of bacterial infections. Quinoxaline 1,4-dioxides represent a prospective scaffold for search of new compounds with improved chemotherapeutic characteristics. Novel 2-acyl-3-trifluoromethylquinoxaline 1,4-dioxides with alteration of substituents at position 2 and 6 were synthesized via nucleophilic substitution with piperazine moiety and evaluated against a broad panel of bacteria and fungi by measuring their minimal inhibitory concentrations. Their mode of action was assessed by whole-genomic sequencing of spontaneous drug-resistant Mycobacterium smegmatis mutants, followed by comparative genomic analysis, and on an original pDualrep2 system. Most of the 2-acyl-3-trifluoromethylquinoxaline 1,4-dioxides showed high antibacterial properties against Gram-positive strains, including mycobacteria, and the introduction of a halogen atom in the position 6 of the quinoxaline ring further increased their activity, with 13c being the most active compound. The mode of action studies confirmed the DNA-damaging nature of the obtained quinoxaline 1,4-dioxides, while drug-resistance may be provided by mutations in redox homeostasis genes, encoding enzymes potentially involved in the activation of the compounds. This study extends views about the antimicrobial and antifungal activities of the quinoxaline 1,4-dioxides and can potentially lead to the discovery of new antibacterial drugs.

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Section: Mechanism Of Action Determinationmentioning

confidence: 65%

“…As it has been previously shown, that DIOX induces SOS-response in bacterial cells [37], the mechanism of antibacterial activity of novel 3-trifluoromethylquinoxaline 1,4-dioxides was analyzed by means of the pDualrep2 reported system [38]. In this reporter expression, turboRFP gene is under regulation of sulA promoter and upregulated in the presence of SOS-response inducers (topoisomerase inhibitors, DNA-intercalators etc), while Katu-shka2S is expressed in the presence of translation inhibitors, due to the stalling of the ribosomes at the modified TrpL leader peptide which leads to transcription antitermination.…”

Section: Mechanism Of Action Determinationmentioning

confidence: 65%

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Synthesis and Characterization of Novel 2-Acyl-3-trifluoromethylquinoxaline 1,4-Dioxides as Potential Antimicrobial Agents

et al. 2022

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“…After the primary screening on biosensors, we tested their effect directly on the model of ciprifloxacin-induced resistance to rifampicin. Such processes of cross-induced resistance, as it were shown before [31], might be the part of a global problem ob antibiotic resistance. The proposed test system allows one to immediately determine the potential of the studied inhibitor in preventing the adaptation of bacteria to antimicrobial agents.…”

Section: Discussionmentioning

confidence: 83%

Extracts of medical plants suppress the SOS response and reduce mutagenesis in E. coli

et al. 2020

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One of the promising directions in the fight against the emergence and spread of farm animal microbiota resistance factors is the development and search for feed additives that can inhibit the SOSresponse. SOS-response is one of the main mechanisms of the occurrence of mutations in bacteria. Plants used in traditional medicine can be a promising source of safe substances that reduce the SOS-response of bacteria. A screening of plants potentially containing substances with antiSOS activity was performed. During the initial screening, the E. coli MG 1655 pRecA-lux biosensor strain with ciprofloxacin as RecA inducer was used. Seven plants were identified whose extracts reduced the expression of the RecA operon. In further experiments on bacteria exposed to antibiotics, we identified four plants whose exstracts significantly reduced the mutagenesis rate of clinical E. coli strains: Austrian broom (Cytisus austriacus), greater celandine (Chelidonium majus), walnut (Juglans regia) and smooth sumac (Rhus glabra).

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“…Dioxidine was used as an inducer of genotoxic stress at a concentration of 2.25 × 10 -5 M, an antibacterial drug with a DNA-damaging mechanism of action due to the generation of reactive oxygen species, including superoxide (31) and, possibly, hydrogen peroxide (32); inducers of oxidative stress - hydrogen peroxide 10 -3 M and paraquat 10 -3 M, under aerobic conditions causing the formation of superoxide radical O 2- (33).…”

Section: Methodsmentioning

confidence: 99%

Solubilizer of Bacterial Origin Surfactin Increases the Biological Activity of C60 Fullerene

Emelyantsev,

Prazdnova,

Chistyakov

2023

Preprint

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Currently, there exists conflicting data regarding the biological activity of unmodified fullerene C60. Various sources report its toxicity, geroprotective activity, and potential interaction with DNA. Contradictory findings regarding the toxicity of C60may arise from the use of toxic solvents, as well as the influence of bioavailability and bioactivity on the preparation conditions of C60suspensions. Furthermore, the microbiota of experimental animals can impact geroprotective activity results by releasing surfactants that facilitate substance penetration through the cell membrane.In this study, we selected conditions for solubilizing fullerene C60in a solution of surfactin, a surfactant of bacterial origin, as well as in a 2% aqueous solution of TWEEN 80, employing ultrasound. Through bioluminescent analysis using lux biosensors in E. coli MG1655, we observed that C60in surfactin reduced induced genotoxic and oxidative stress. Given that surfactin enhances membrane permeability to fullerene C60, suspensions of fullerene in designated concentrations of surfactin can be regarded as a DNA protector and antioxidant, warranting further investigation as a promising component of novel drugs.

show abstract

Dioxidine induces bacterial resistance to antibiotics

Cited by 6 publications

References 6 publications

Synthesis and Characterization of Novel 2-Acyl-3-trifluoromethylquinoxaline 1,4-Dioxides as Potential Antimicrobial Agents

Synthesis and Characterization of Novel 2-Acyl-3-trifluoromethylquinoxaline 1,4-Dioxides as Potential Antimicrobial Agents

Extracts of medical plants suppress the SOS response and reduce mutagenesis in E. coli

Solubilizer of Bacterial Origin Surfactin Increases the Biological Activity of C60 Fullerene

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