Atomic-engineering Au-Ag nanoalloys for screening antimicrobial agents with low toxicity towards mammalian cells

Background: The increasing incidence of invasive forms of candidiasis and resistance to antifungal therapy leads us to seek new and more effective antifungal compounds. Objective: To investigate the antifungal activity and toxicity as well as to evaluate the potential targets of 2- cyclohexylidenhydrazo-4-phenyl-thiazole (CPT) in Candida albicans. Methods: The antifungal activity of CPT against the survival of C. albicans was investigated in Caenorhabditis elegans. Additionally, we determined the effect of CPT on the inhibition of C. albicans adhesion capacity to buccal epithelial cells (BECs), the toxicity of CPT in mammalian cells, and the potential targets of CPT in C. albicans. Results: CPT exhibited a minimum inhibitory concentration (MIC) value of 0.4-1.9 µg/mL. Furthermore, CPT at high concentrations (>60 x MIC) showed no or low toxicity in HepG2 cells and <1% haemolysis in human erythrocytes. In addition, CPT decreased the adhesion capacity of yeasts to the BECs and prolonged the survival of C. elegans infected with C. albicans. Analysis of CPT-treated cells showed that their cell wall was thinner than that of untreated cells, especially the glucan layer. We found that there was a significantly lower quantity of 1,3-β-D-glucan present in CPT-treated cells than that in untreated cells. Assays performed on several mutant strains showed that the MIC value of CPT was high for its antifungal activity on yeasts with defective 1,3-β-glucan synthase. Conclusion: In conclusion, CPT appears to target the cell wall of C. albicans, exhibits low toxicity in mammalian cells, and prolongs the survival of C. elegans infected with C. albicans.

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Physics Comes to the Aid of Medicine—Clinically-Relevant Microorganisms through the Eyes of Atomic Force Microscope

Pathogens ◽

10.3390/pathogens9110969 ◽

2020 ◽

Vol 9 (11) ◽

pp. 969

Author(s):

Mateusz Cieśluk ◽

Piotr Deptuła ◽

Ewelina Piktel ◽

Krzysztof Fiedoruk ◽

Łukasz Suprewicz ◽

...

Keyword(s):

Mammalian Cells ◽

Antimicrobial Agents ◽

Antimicrobial Treatment ◽

Point Of View ◽

Diagnostic Methods ◽

Drug Resistant ◽

Bacterial Strains ◽

Force Microscopy ◽

Atomic Force ◽

Recent Developments

Despite the hope that was raised with the implementation of antibiotics to the treatment of infections in medical practice, the initial enthusiasm has substantially faded due to increasing drug resistance in pathogenic microorganisms. Therefore, there is a need for novel analytical and diagnostic methods in order to extend our knowledge regarding the mode of action of the conventional and novel antimicrobial agents from a perspective of single microbial cells as well as their communities growing in infected sites, i.e., biofilms. In recent years, atomic force microscopy (AFM) has been mostly used to study different aspects of the pathophysiology of noninfectious conditions with attempts to characterize morphological and rheological properties of tissues, individual mammalian cells as well as their organelles and extracellular matrix, and cells’ mechanical changes upon exposure to different stimuli. At the same time, an ever-growing number of studies have demonstrated AFM as a valuable approach in studying microorganisms in regard to changes in their morphology and nanomechanical properties, e.g., stiffness in response to antimicrobial treatment or interaction with a substrate as well as the mechanisms behind their virulence. This review summarizes recent developments and the authors’ point of view on AFM-based evaluation of microorganisms’ response to applied antimicrobial treatment within a group of selected bacteria, fungi, and viruses. The AFM potential in development of modern diagnostic and therapeutic methods for combating of infections caused by drug-resistant bacterial strains is also discussed.

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Antimicrobial Peptide-Templated Silver Nanoclusters with Membrane Activity for Enhanced Bacterial Killing

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2020.17161 ◽

2020 ◽

Vol 20 (3) ◽

pp. 1425-1433 ◽

Cited By ~ 1

Author(s):

Xingshu Fei ◽

Xiaochuan Ma ◽

Ge Fang ◽

Yu Chong ◽

Xin Tian ◽

...

Keyword(s):

Antimicrobial Activity ◽

Mammalian Cells ◽

Energy Production ◽

Antimicrobial Agents ◽

Silver Nanoclusters ◽

Bacterial Membrane ◽

Respiratory Chain Complexes ◽

Bacterial Killing ◽

Chain Complexes ◽

Ros Accumulation

We aimed to develop antimicrobial agents that satisfy biosafety considerations while exhibiting efficient antimicrobial activity. Peptide-capped silver nanoclusters (peptide@AgNCs) were designed. In addition, the antimicrobial activity and mechanism of peptide@AgNCs were studied. The hemolysis and cytotoxicity tests on mammalian cells were used to confirm the biocompatibility of peptide@ AgNCs. KLA@AgNCs exhibited dramatic antimicrobial activity without inducing significant cytotoxicity in mammalian cells. The KLA@AgNCs destroyed the integrity of the bacterial membrane and induced ROS accumulation, causing oxidative damage to biomolecules. The malfunction of the respiratory chain complexes I and V completely suppresses the energy production, ultimately accelerating the death of the bacteria. Our findings may advance the development of Ag-based nanomaterials with enhanced bactericidal activity and improved biocompatibility.

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An unexpected discovery toward novel membrane active sulfonyl thiazoles as potential MRSA DNA intercalators

Future Medicinal Chemistry ◽

10.4155/fmc-2019-0303 ◽

2020 ◽

Vol 12 (19) ◽

pp. 1709-1727 ◽

Cited By ~ 1

Author(s):

Yuan-Yuan Hu ◽

Juan Wang ◽

Tie-Jun Li ◽

Rammohan R Yadav Bheemanaboina ◽

Mohammad Fawad Ansari ◽

...

Keyword(s):

Mammalian Cells ◽

Antibacterial Agents ◽

Antimicrobial Agents ◽

Methicillin Resistant Staphylococcus Aureus ◽

Inhibitory Concentration ◽

Resistant Bacteria ◽

Drug Resistant ◽

Dna Intercalators ◽

Dna Targeting ◽

Drug Resistant Bacteria

Aim: With the increasing emergence of drug-resistant bacteria, the need for new antimicrobial agents has become extremely urgent. This work was to develop sulfonyl thiazoles as potential antibacterial agents. Results & methodology: Novel hybrids of sulfonyl thiazoles were developed from commercial acetanilide and acetylthiazole. Hybrids 6e and 6f displayed excellent inhibitory efficacy against clinical methicillin-resistant Staphylococcus aureus (MRSA) (minimum inhibitory concentration = 1 μg/ml) without obvious toxicity toward normal mammalian cells (RAW 264.7). The combination uses were found to improve the antimicrobial ability. Further preliminary antibacterial mechanism experiments showed that the active molecule 6f could effectively interfere with MRSA membrane and insert into MRSA DNA. Conclusion: Compounds 6e and 6f could serve as potential DNA-targeting templates toward the development of promising antimicrobial agents.

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Arene–Ru(II)–chloroquine complexes interact with DNA, induce apoptosis on human lymphoid cell lines and display low toxicity to normal mammalian cells

Journal of Inorganic Biochemistry ◽

10.1016/j.jinorgbio.2010.05.002 ◽

2010 ◽

Vol 104 (9) ◽

pp. 967-977 ◽

Cited By ~ 40

Author(s):

Alberto Martínez ◽

Chandima S.K. Rajapakse ◽

Roberto A. Sánchez-Delgado ◽

Armando Varela-Ramirez ◽

Carolina Lema ◽

...

Keyword(s):

Cell Lines ◽

Lymphoid Cell ◽

Mammalian Cells ◽

Human Lymphoid Cell ◽

Low Toxicity ◽

Lymphoid Cell Lines

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A Safe and Multitasking Antimicrobial Decapeptide: The Road from De Novo Design to Structural and Functional Characterization

International Journal of Molecular Sciences ◽

10.3390/ijms21186952 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6952

Author(s):

Bruna Agrillo ◽

Yolande T. R. Proroga ◽

Marta Gogliettino ◽

Marco Balestrieri ◽

Rosarita Tatè ◽

...

Keyword(s):

Mammalian Cells ◽

Fungal Pathogens ◽

Antimicrobial Agents ◽

De Novo ◽

Low Cost ◽

Functional Characterization ◽

Human Keratinocytes ◽

Minimal Bactericidal Concentration ◽

Microbial Spoilage ◽

Structural Resistance

Antimicrobial peptides (AMPs) are excellent candidates to fight multi-resistant pathogens worldwide and are considered promising bio-preservatives to control microbial spoilage through food processing. To date, designing de novo AMPs with high therapeutic indexes, low-cost synthesis, high resistance, and bioavailability, remains a challenge. In this study, a novel decapeptide, named RiLK1, was rationally designed starting from the sequence of the previously characterized AMP 1018-K6, with the aim of developing short peptides, and promoting higher selectivity over mammalian cells, antibacterial activity, and structural resistance under different salt, pH, and temperature conditions. Interestingly, RiLK1 displayed a broad-spectrum of bactericidal activity against Gram-positive and Gram-negative bacteria, including multidrug resistant clinical isolates of Salmonella species, with Minimal Bactericidal Concentration (MBC) values in low micromolar range, and it was effective even against two fungal pathogens with no evidence of cytotoxicity on human keratinocytes and fibroblasts. Moreover, RiLK1-activated polypropylene films were revealed to efficiently prevent the growth of microbial spoilage, possibly improving the shelf life of fresh food products. These results suggested that de novo designed peptide RiLK1 could be the first candidate for the development of a promising class of decameric and multitask antimicrobial agents to overcome drug-resistance phenomena.

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Genetic and Phenotypic Identification of Fusidic Acid-Resistant Mutants with the Small-Colony-Variant Phenotype in Staphylococcus aureus

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00328-07 ◽

2007 ◽

Vol 51 (12) ◽

pp. 4438-4446 ◽

Cited By ~ 65

Author(s):

Tobias Norström ◽

Jonas Lannergård ◽

Diarmaid Hughes

Keyword(s):

Staphylococcus Aureus ◽

Fusidic Acid ◽

Mammalian Cells ◽

Antimicrobial Agents ◽

Structural Domain ◽

Small Colony ◽

Resistant Mutants ◽

Substitution Mutations ◽

Domain V ◽

Domain I

ABSTRACT Small-colony variants (SCVs) of Staphylococcus aureus are a slow-growing subpopulation whose phenotypes can include resistance to aminoglycosides, defects in electron transport, and enhanced persistence in mammalian cells. Here we show that a subset of mutants selected as SCVs by reduced susceptibility to aminoglycosides are resistant to the antibiotic fusidic acid (FA) and conversely that a subset of mutants selected for resistance to FA are SCVs. Mutation analysis reveals different genetic classes of FA-resistant SCVs. One class, FusA-SCVs, have amino acid substitution mutations in the ribosomal translocase EF-G different from those found in classic FusA mutants. Most of these mutations are located in structural domain V of EF-G, but some are in domain I or III. FusA-SCVs are auxotrophic for hemin. A second class of FA-resistant SCVs carry mutations in rplF, coding for ribosomal protein L6, and are designated as FusE mutants. FusE mutants fall into two phenotypic groups: one auxotrophic for hemin and the other auxotrophic for menadione. Accordingly, we have identified new genetic and phenotypic classes of FA-resistant mutants and clarified the genetic basis of a subset of S. aureus SCV mutants. A clinical implication of these data is that FA resistance could be selected by antimicrobial agents other than FA.

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Аntibacterial inorganic agents: efficiency of using multicomponent systems

Russian Journal of Infection and Immunity ◽

10.15789/2220-7619-aia-1512 ◽

2020 ◽

Vol 10 (4) ◽

pp. 639-654

Author(s):

А. A. Meleshko ◽

A. G. Afinogenova ◽

G. E. Afinogenov ◽

A. A. Spiridonova ◽

V. P. Tolstoy

Keyword(s):

Antimicrobial Activity ◽

Antibacterial Activity ◽

Antimicrobial Agents ◽

Metal Oxide Nanoparticles ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Nanoscale Systems ◽

Gram Negative ◽

Low Toxicity

Metal and metal oxide nanoparticles (NPs) are promising antibacterial agents. They have a broad antimicrobial activity against both Gram-positive and Gram-negative bacteria, viruses, and protozoans. The use of NPs reduces the possibility of the microbial resistance development. This review briefly shows the general mechanisms and the main factors of antibacterial activity of NPs. In this article, a comprehensive review of the recent researches in the field of new antimicrobial agents with superior long-term bactericidal activity and low toxicity is provided. The review gives the examples of synthesis of double and triple nanocomposites based on following oxides: CuO, ZnO, Fe3O4, Ag2O, MnO2, etc. including metal and nonmetal doped nanocomposites (for example with Ag, Ce, Cr, Mn, Nd, Co, Sn, Fe, N, F, etc.). Compared with bactericidal action of individual oxides, the nanocomposites demonstrate superior antibacterial activity and have synergistic effects. For example, the antimicrobial activity of ZnO against both Gram-positive and Gram-negative bacteria was increased by -100% by formation of triple nanocomposites ZnO—MnO2—Cu2O or ZnO—Ag2O—Ag2S. Similar effect was showed for Ce-doped ZnO and Zn-doped CuO. The present article also provides the examples of nanocomposites containing NPs and organic (chitosan, cellulose, polyvinylpyrrolidone, biopolymers, etc.) or inorganic materials with special structure (graphene oxide, TiO2 nanotubes, silica) which demonstrate controlled release and longterm antibacterial activity. All of the considered nanocomposites and their combinations have a pronounced long-term antimicrobial effect including against antibiotic-resistant strains. They are able to prevent the formation of microbial biofilms on biotic and abiotic surfaces, have low toxicity to eukaryotic cells, demonstrate anti-inflammatory and woundhealing properties in compositions with polymers (sodium alginate, collagen, polyvinylpyrrolidone, etc.). The use of nanoscale systems can solve several important practical problems at the same time: saving of long-term antimicrobial activities while reducing the number of compounds, creation of new antimicrobial agents with low toxicity and reduced environmental impact, development of new biocidal materials, including new coatings for effective antimicrobial protection of medical devices.

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Use of fluoroquinolones in practice of veterinary medicine of Ukraine

Scientific Messenger of LNU of Veterinary Medicine and Biotechnology ◽

10.15421/nvlvet8718 ◽

2018 ◽

Vol 20 (87) ◽

pp. 89-93

Author(s):

N. Slobodyuk

Keyword(s):

Veterinary Medicine ◽

Bacterial Infection ◽

Antimicrobial Agents ◽

Bactericidal Effect ◽

Pharmacokinetic Properties ◽

Low Toxicity ◽

Resistant Strains ◽

Livestock Products ◽

Fur Animals ◽

Fluoroquinolone Group

Antibacterial agents are one of the most important groups of medical preparations in the treatment of bacterial infection of different localization in humane and in veterinary medicine. The consequence of their rational use (the establishment of sensitivity of the pathogenic microflora, compliance with the course of treatment, etc.) have a high therapeutic effect and the minimum development of resistant strains of microorganisms. The widely used group of antimicrobial agents in veterinary medicine are second-generation fluorohinolone antibiotics that have good pharmacokinetic properties, a broad spectrum of bactericidal activity, and relatively low toxicity, although they have their own warnings and restrictions on the use of small animals during the formation of bone tissue. To achieve high therapeutic efficacy and minimizing of side effects, it is described the compatibility of some fluoroquinolones with other pharmacological groups. They found their application in the treatment of both productive animals, poultry, fur animals and petty domestic (dogs and cats) with a bacterial infection of the urinary tract, digestive and respiratory systems, infected wounds, etc. The article describes the detailed mechanism of action of the antibiotics of the fluoroquinolone group, which provides an opportunity for a deeper understanding of the manifestation of the bactericidal effect, as well as their classification by generation or generation. Particular attention deserves attention to the time of carrenia of fluoroquinolones in the context of their application to productive animals, because high quality livestock products minimize the development of resistant strains in humans and provide them with health. There is also a list of all registered medicinal products registered in Ukraine containing: ofloxacin, enrofloxacin, ciprofloxacin, marbofloxacin, denofloxacin, which carries important informative information for practicing doctors, pharmacists, etc.

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Self-assembly of a novel Cu(ii) coordination complex forms metallo-vesicles that are able to transfect mammalian cells

New Journal of Chemistry ◽

10.1039/c7nj02161e ◽

2017 ◽

Vol 41 (19) ◽

pp. 11230-11237 ◽

Cited By ~ 4

Author(s):

Sarit Pal ◽

Md Tariqul Islam ◽

James T. Moore ◽

Jesus Reyes ◽

Andrew Pardo ◽

...

Keyword(s):

Self Assembly ◽

Mammalian Cells ◽

Gene Transfection ◽

Coordination Complex ◽

Low Toxicity ◽

Complex Forms

Coordination-directed self-assembly of a Cu(ii) amphiphilic complex forms homogeneous nanometer-sized metallo-vesicles in water with low toxicity and gene transfection properties.

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