Dataset Information

Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF₆) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.

ABSTRACT: Antibiotic resistance is becoming a global scourge with 700,000 deaths each year and could cause up to 10 million deaths by 2050. As an example, Staphylococcus epidermidis has emerged as a causative agent of infections often associated with implanted medical devices. S. epidermidis can form biofilms, which contribute to its pathogenicity when present in intravascular devices. These staphylococci, embedded in the biofilm matrix, are resistant to methicillin, which had long been the recommended therapy and which has nowadays been replaced by less toxic and more stable therapeutic agents. Moreover, current reports indicate that 75 to 90% of Staphylococcus epidermidis isolates from nosocomial infections are methicillin-resistant strains. The challenge of successfully combating antibiotics resistance in biofilms requires the use of compounds with a controlled mode of action that can act in combination with antibiotics. Ruthenium nitrosyl complexes are potential systems for NO release triggered by light. The influence of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF₆) on Staphylococcus epidermidis resistant to methicillin is described. The results show a 50% decrease in cell viability in bacteria treated with low concentrations of NO. When combined with methicillin, this low dose of NO dramatically decreases bacterial resistance and makes bacteria 100-fold more sensitive to methicillin.

SUBMITTER: Boce M

PROVIDER: S-EPMC6424994 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF<sub>6</sub>) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.

Bocé Mathilde M Tassé Marine M Mallet-Ladeira Sonia S Pillet Flavien F Da Silva Charlotte C Vicendo Patricia P Lacroix Pascal G PG Malfant Isabelle I Rols Marie-Pierre MP

Scientific reports 20190319 1

Antibiotic resistance is becoming a global scourge with 700,000 deaths each year and could cause up to 10 million deaths by 2050. As an example, Staphylococcus epidermidis has emerged as a causative agent of infections often associated with implanted medical devices. S. epidermidis can form biofilms, which contribute to its pathogenicity when present in intravascular devices. These staphylococci, embedded in the biofilm matrix, are resistant to methicillin, which had long been the recommended th ...[more]

PMID: 30890745

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Project description:Staphylococcus epidermidis is part of the normal microbiota that colonizes the skin and mucosal surfaces of human beings. Previous studies suggested that S. epidermidis possessed low virulence, but recent studies confirmed that it can acquire high virulence from Staphylococcus aureus and with the increasing detection of methicillin-resistant S. epidermidis. It has become a major pathogen of graft-associated and hospital-acquired infections. In previous studies, we modified the antimicrobial peptide Cec4 (41 amino acids) and obtained the derived peptide C9 (16 amino acids) showing better antimicrobial activity against S. epidermidis with an MIC value of 8 μg/mL. The peptide has rapid bactericidal activity without detectable high-level resistance, showing certain inhibition and eradication ability on S. epidermidis biofilms. The damage of cell membrane structures by C9 was observed by scanning emission microscopy (SEM) and transmission electron microscopy (TEM). In addition, C9 altered the S. epidermidis cell membrane permeability, depolarization levels, fluidity, and reactive oxygen species (ROS) accumulation and possessed the ability to bind genomic DNA. Analysis of the transcriptional profiles of C9-treated cells revealed changes in genes involved in cell wall and ribosome biosynthesis, membrane protein transport, oxidative stress, and DNA transcription regulation. At the same time, the median lethal dose of C9 in mice was more than 128 mg/kg, and the intraperitoneal administration of 64 mg/kg was less toxic to the liver and kidneys of mice. Furthermore, C9 also showed a certain therapeutic effect on the mouse bacteremia model. In conclusion, C9 may be a candidate drug against S. epidermidis, which has the potential to be further developed as an antibacterial therapeutic agent. IMPORTANCE S. epidermidis is one of the most important pathogens of graft-related infection and hospital-acquired infection. The growing problem of antibiotic resistance, as well as the emergence of bacterial pathogenicity, highlights the need for antimicrobials with new modes of action. Antimicrobial peptides have been extensively studied over the past 30 years as ideal alternatives to antibiotics, and we report here that the derived peptide C9 is characterized by rapid bactericidal and antibiofilm activity, avoiding the development of resistance by acting on multiple nonspecific targets of the cell membrane or cell components. In addition, it has therapeutic potential against S. epidermidis infection in vivo. This study provides a rationale for the further development and application of C9 as an effective candidate antibiotic.

Project description:Synthesis and X-ray diffraction structures of cis and trans isomers of ruthenium and osmium metal complexes of general formulas (nBu4N)[cis-MCl4(NO)(Hind)], where M = Ru (1) and Os (3), and (nBu4N)[trans-MCl4(NO)(Hind)], where M = Ru (2) and Os (4) and Hind = 1H-indazole are reported. Interconversion between cis and trans isomers at high temperatures (80-130 °C) has been observed and studied by NMR spectroscopy. Kinetic data indicate that isomerizations correspond to reversible first order reactions. The rates of isomerization reactions even at 110 °C are very low with rate constants of 10(-5) s(-1) and 10(-6) s(-1) for ruthenium and osmium complexes, respectively, and the estimated rate constants of isomerization at room temperature are of ca. 10(-10) s(-1). The activation parameters, which have been obtained from fitting the reaction rates at different temperatures to the Eyring equation for ruthenium [?H(cis-trans)‡ = 122.8 ± 1.3; ?H(trans-cis)‡ = 138.8 ± 1.0 kJ/mol; ?S(cis-trans)‡ = -18.7 ± 3.6; ?S(trans-cis)‡ = 31.8 ± 2.7 J/(mol·K)] and osmium [?H(cis-trans)‡ = 200.7 ± 0.7; ?H(trans-cis)‡ = 168.2 ± 0.6 kJ/mol; ?S(cis-trans)‡ = 142.7 ± 8.9; ?S(trans-cis)‡ = 85.9 ± 3.9 J/(mol·K)] reflect the inertness of these systems. The entropy of activation for the osmium complexes is highly positive and suggests the dissociative mechanism of isomerization. In the case of ruthenium, the activation entropy for the cis to trans isomerization is negative [-18.6 J/(mol·K)], while being positive [31.0 J/(mol·K)] for the trans to cis conversion. The thermodynamic parameters for cis to trans isomerization of [RuCl4(NO)(Hind)]-, viz. ?H° = 13.5 ± 1.5 kJ/mol and ?S° = -5.2 ± 3.4 J/(mol·K) indicate the low difference between the energies of cis and trans isomers. The theoretical calculation has been carried out on isomerization of ruthenium complexes with DFT methods. The dissociative, associative, and intramolecular twist isomerization mechanisms have been considered. The value for the activation energy found for the dissociative mechanism is in good agreement with experimental activation enthalpy. Electrochemical investigation provides further evidence for higher reactivity of ruthenium complexes compared to that of osmium counterparts and shows that intramolecular electron transfer reactions do not affect the isomerization process. A dissociative mechanism of cis?trans isomerization has been proposed for both ruthenium and osmium complexes.

Dataset Information

Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF₆) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.

Publications

Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF<sub>6</sub>) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.

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Dataset Information

Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF6) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.

Publications

Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF<sub>6</sub>) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Effect of trans(NO, OH)-[RuFT(Cl)(OH)NO](PF₆) ruthenium nitrosyl complex on methicillin-resistant Staphylococcus epidermidis.