Gram-positive bacteria are responsible for a wide range of infections in humans. In most Gram-positive bacteria, sortase A plays a significant role in attaching virulence factors to the bacteria's cell wall. These cell surface proteins play a significant role in virulence and pathogenesis. Even though antibiotics are available to treat these infections, there is a continuous search for an alternative strategy due to an increase in antibiotic resistance. Thus, using anti-sortase drugs to combat these bacterial infections may be a promising approach. Here, we describe a method for targeting Gram-positive bacterial infection by combining curcumin and trans-chalcone as sortase A inhibitors. We have used curcumin and trans-chalcone alone and in combination as a sortase A inhibitor. We have seen ~78%, ~43%, and ~94% inhibition when treated with curcumin, trans-chalcone, and a combination of both compounds, respectively. The compounds have also shown a significant effect on biofilm formation, IgG binding, protein A recruitment, and IgG deposition. We discovered that combining curcumin and trans-chalcone is more effective against Gram-positive bacteria than either compound alone. The present work demonstrated that a combination of these natural compounds could be used as an antivirulence therapy against Gram-positive bacterial infection.
- MeSH
- aminoacyltransferasy * antagonisté a inhibitory metabolismus MeSH
- antibakteriální látky * farmakologie chemie MeSH
- bakteriální proteiny * metabolismus antagonisté a inhibitory MeSH
- biofilmy * účinky léků MeSH
- chalkon * farmakologie chemie MeSH
- cysteinové endopeptidasy * metabolismus MeSH
- faktory virulence metabolismus MeSH
- grampozitivní bakteriální infekce farmakoterapie mikrobiologie MeSH
- grampozitivní bakterie účinky léků MeSH
- kurkumin * farmakologie chemie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- virulence účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Nanoparticles have drawn significant interest in a range of applications, ranging from biomedical to environmental sciences, due to their distinctive physicochemical characteristics. In this study, it was reported that simple biological production of Ag, Se, and bimetallic Ag2Se nanoparticles (NPs) with Pseudomonas aeruginosa is a promising, low-cost, and environmentally friendly method. For the first time in the scientific literature, Ag2Se nanoparticles have been generated via green bacterial biosynthesis. UV-vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and EDX were used to characterize the produced NPs. Biosynthesized NPs were examined for antibacterial, antibiofilm, and photocatalytic properties, and it was determined that the effects of NPs were dose dependent. The biosynthesized AgNPs, SeNPs, and Ag2Se NPs showed anti-microbial activity against Escherichia coli and Staphylococcus aureus. Minimal inhibitory concentrations (MICs) of E. coli and S. aureus were between 150 and 250 μg/mL. The NPs showed antibiofilm activity against E. coli and S. aureus at sub-MIC levels and reduced biofilm formation by at least 80% at a concentration of 200 μg/mL of each NPs. To photocatalyze the breakdown of Congo red, Ag, Se, and Ag2Se NPs were utilized, and their photocatalytic activity was tested at various concentrations and intervals. A minor decrease of photocatalytic degradation was detected throughout the NPs reuse operation (five cycles). Based on the encouraging findings, the synthesized NPs demonstrated antibacterial, antibiofilm, and photocatalytic properties, suggesting that they might be used in pharmaceutical, medical, environmental, and other applications.
- MeSH
- antibakteriální látky * farmakologie chemie chemická syntéza MeSH
- biofilmy * účinky léků MeSH
- Escherichia coli * účinky léků MeSH
- katalýza MeSH
- kovové nanočástice * chemie MeSH
- mikrobiální testy citlivosti * MeSH
- Pseudomonas aeruginosa * účinky léků metabolismus MeSH
- selen chemie farmakologie MeSH
- sloučeniny stříbra chemie farmakologie MeSH
- Staphylococcus aureus * účinky léků MeSH
- stříbro * chemie farmakologie metabolismus MeSH
- technologie zelené chemie * MeSH
- Publikační typ
- časopisecké články MeSH
ETHNOPHARMACOLOGICAL RELEVANCE: Paulownia tomentosa Steud. (P. tomentosa) is a medium-sized tree traditionally used in Chinese folk medicine for the treatment of infectious diseases. It is a rich source of prenylated phenolic compounds that have been extensively studied for their promising biological activities. AIM OF THE STUDY: Due to the increasing development of antibiotic resistance, our study investigated plant-derived natural products from the fruits of P. tomentosa that could control Staphylococcus aureus infections with novel targets/modes of action and reduce antimicrobial resistance. MATERIALS AND METHODS: The ethanolic extract was fractionated and detected by liquid chromatography. The antistaphylococcal effects of the plant formulations were studied in detail in vitro by various biological methods, including microdilution methods for minimum inhibitory concentration (MIC), the checkerboard titration technique for synergy assay, fluorescence measurements for membrane disruption experiments, autoinducer-2-mediated bioassay for quorum sensing inhibition, and counting of colony-forming units for relative adhesion. Morphology was examined by transmission electron microscopy. RESULTS: Total ethanolic extract and chloroform fraction showed MICs of 128 and 32 μg/mL, respectively. Diplacol, diplacone, and 3'-O-methyl-5'-hydroxydiplacone inhibited S. aureus growth in the range of 8-16 μg/mL. Synergistic potential was shown in combination with mupirocin and fusidic acid. The ethanolic extract and the chloroform fraction destroyed the cell membranes by 91.61% and 79.46%, respectively, while the pure compounds were less active. The ethanolic extract and the pure compounds reduced the number of adhered cells to 47.33-10.26% compared to the untreated control. All tested plant formulations, except diplacone, inhibited quorum sensing of S. aureus. Transmission electron microscopy showed deformation of S. aureus cells. CONCLUSIONS: The products from the fruit of P. tomentosa showed antimicrobial properties against S. aureus alone and in combination with antibiotics. By affecting intracellular targets, geranylated flavonoids proposed novel approaches in the control of staphylococcal infections.
- MeSH
- antibakteriální látky chemie MeSH
- antiinfekční látky * farmakologie MeSH
- chloroform MeSH
- ethanol farmakologie MeSH
- hluchavkotvaré * MeSH
- mikrobiální testy citlivosti MeSH
- ovoce chemie MeSH
- rostlinné extrakty chemie MeSH
- stafylokokové infekce * MeSH
- Staphylococcus aureus MeSH
- Publikační typ
- časopisecké články MeSH
Wound healing is a complex process; therefore, new dressings are frequently required to facilitate it. In this study, porous bacterial levan-based sponges containing cannabis oil (Lev@CBDs) were prepared and fully characterized. The sponges exhibited a suitable swelling ratio, proper water vapor transmission rate, sufficient thermal stability, desired mechanical properties, and good antioxidant and anti-inflammatory properties. The obtained Lev@CBD materials were evaluated in terms of their interaction with proteins, human serum albumin and fibrinogen, of which fibrinogen revealed the highest binding effect. Moreover, the obtained biomaterials exhibited antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa, as well as being non-hemolytic material as indicated by hemolysis tests. Furthermore, the sponges were non-toxic and compatible with L929 mouse fibroblasts and HDF cells. Most significantly, the levan sponge with the highest content of cannabis oil, in comparison to others, retained its non-hemolytic, anti-inflammatory, and antimicrobial properties after prolonged storage in a climate chamber at a constant temperature and relative humidity. The designed sponges have conclusively proven their beneficial physicochemical properties and, at the preliminary stage, biocompatibility as well, and therefore can be considered a promising material for wound dressings in future in vivo applications.
- MeSH
- antibakteriální látky farmakologie chemie MeSH
- antiflogistika MeSH
- chitosan * chemie MeSH
- fibrinogen MeSH
- lidé MeSH
- myši MeSH
- obvazy MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The ribosome is a major target for clinically used antibiotics, but multidrug resistant pathogenic bacteria are making our current arsenal of antimicrobials obsolete. Here we present cryo-electron-microscopy structures of 17 distinct compounds from six different antibiotic classes bound to the bacterial ribosome at resolutions ranging from 1.6 to 2.2 Å. The improved resolution enables a precise description of antibiotic-ribosome interactions, encompassing solvent networks that mediate multiple additional interactions between the drugs and their target. Our results reveal a high structural conservation in the binding mode between antibiotics with the same scaffold, including ordered water molecules. Water molecules are visualized within the antibiotic binding sites that are preordered, become ordered in the presence of the drug and that are physically displaced on drug binding. Insight into RNA-ligand interactions will facilitate development of new antimicrobial agents, as well as other RNA-targeting therapies.
In the current epoch, noble metals/metal oxides with precise structures are needed to develop sustainable products to improve the welfare of human beings and the environment. Nanomaterials in the regime 1 -100 nm scale are a promising material for the research fraternities owing to their stupendous properties. The metallic/metal oxide nanoparticles (silver, gold, copper oxide, iron oxide, magnesium oxide) are gaining significant momentum and need to be extensively studied. Magnesium oxide nanoparticles (MgONPs) are a periclase, white hygroscopic material consisting of Mg2+ ions and O-2 ions in lattice arranged. These nanoparticles can be fabricated through physical, chemical and biological methods. The development of green synthesized MgONPs needs to be ascertained and explored its ultimate in medicine, health, cosmetics, environmental protection, chemical industries, and energy. Therefore, the present review manifests the green synthetic approaches of MgONPs and their impact on crystalline structure and shape. Further, we have provided the antibacterial and anticancer activities of MgONPs thoroughly reported in various kinds of literature. Overall, the unique MgONPs can be plausibly used as safe biomaterials in biomedical applications.
- MeSH
- antibakteriální látky farmakologie chemie MeSH
- kovové nanočástice * chemie MeSH
- lidé MeSH
- nanostruktury * MeSH
- oxid hořečnatý farmakologie chemie MeSH
- oxidy chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
In this study, we have focused on a multiparametric microbiological analysis of the antistaphylococcal action of the iodinated imine BH77, designed as an analogue of rafoxanide. Its antibacterial activity against five reference strains and eight clinical isolates of Gram-positive cocci of the genera Staphylococcus and Enterococcus was evaluated. The most clinically significant multidrug-resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant S. aureus (VRSA), and vancomycin-resistant Enterococcus faecium, were also included. The bactericidal and bacteriostatic actions, the dynamics leading to a loss of bacterial viability, antibiofilm activity, BH77 activity in combination with selected conventional antibiotics, the mechanism of action, in vitro cytotoxicity, and in vivo toxicity in an alternative animal model, Galleria mellonella, were analyzed. The antistaphylococcal activity (MIC) ranged from 15.625 to 62.5 μM, and the antienterococcal activity ranged from 62.5 to 125 μM. Its bactericidal action; promising antibiofilm activity; interference with nucleic acid, protein, and peptidoglycan synthesis pathways; and nontoxicity/low toxicity in vitro and in vivo in the Galleria mellonella model were found to be activity attributes of this newly synthesized compound. In conclusion, BH77 could be rightfully minimally considered at least as the structural pattern for future adjuvants for selected antibiotic drugs. IMPORTANCE Antibiotic resistance is among the largest threats to global health, with a potentially serious socioeconomic impact. One of the strategies to deal with the predicted catastrophic future scenarios associated with the rapid emergence of resistant infectious agents lies in the discovery and research of new anti-infectives. In our study, we have introduced a rafoxanide analogue, a newly synthesized and described polyhalogenated 3,5-diiodosalicylaldehyde-based imine, that effectively acts against Gram-positive cocci of the genera Staphylococcus and Enterococcus. The inclusion of an extensive and comprehensive analysis for providing a detailed description of candidate compound-microbe interactions allows the valorization of the beneficial attributes linked to anti-infective action conclusively. In addition, this study can help with making rational decisions about the possible involvement of this molecule in advanced studies or may merit the support of studies focused on related or derived chemical structures to discover more effective new anti-infective drug candidates.
- MeSH
- antibakteriální látky farmakologie chemie MeSH
- antiinfekční látky * farmakologie MeSH
- Enterococcus MeSH
- methicilin rezistentní Staphylococcus aureus * MeSH
- mikrobiální testy citlivosti MeSH
- rafoxanid farmakologie MeSH
- Staphylococcus aureus MeSH
- Staphylococcus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1) and 4-(trifluoromethyl)cinnamic acid (series 2) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2E)-3-[3-(Trifluoromethyl)phenyl]-N-[4-(trifluoromethyl)phenyl]prop-2-enamide (1j), (2E)-N-(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide (1o) and (2E)-N-[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide (2i), (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide (2p) showed antistaphylococcal (MICs/MBCs 0.15-5.57 μM) as well as anti-enterococcal (MICs/MBCs 2.34-44.5 μM) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 μM, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 μM). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p, all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.
A new method for modifying the structure of tetracyclic quinobenzothiazinium derivatives has been developed, allowing introduction of various substituents at different positions of the benzene ring. The method consists of reacting appropriate aniline derivatives with 5,12-(dimethyl)thioquinantrenediinium bis-chloride. A series of new quinobenzothiazine derivatives was obtained with propyl, allyl, propargyl and benzyl substituents in 9, 10 and 11 positions, respectively. The structure of the obtained compounds was analyzed by 1H and 13C NMR (HSQC, HMBC) and X-ray analysis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). In addition, all the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. 9-Benzyloxy-5-methyl-12H-quino [3,4-b][1,4]benzothiazinium chloride (6j), 9-propoxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6a) and 9-allyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6d) demonstrated high activity against the entire tested microbial spectrum. The activities of the compounds were comparable with oxacillin, tetracycline and ciprofloxacinagainst staphylococcal strains and with rifampicin against both mycobacterial strains. Compound 6j had a significant effect on the inhibition of bacterial respiration as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity, but also bactericidal activity. Preliminary in vitro cytotoxicity screening of the compounds performed using normal human dermal fibroblasts (NHDF) proved that the tested compounds showed an insignificant cytotoxic effect on human cells (IC50 > 37 μM), making these compounds interesting for further investigation. Moreover, the intermolecular similarity of novel compounds was analyzed in the multidimensional space (mDS) of the structure/property-related in silico descriptors by means of principal component analysis (PCA) and hierarchical clustering analysis (HCA), respectively. The distance-oriented structure/property distribution was related with the experimental lipophilic data.
Four new depsidones, mollicellins V-Y (1-4), together with eight known depsidones (5-12) were isolated from the endophytic fungus, Chaetomium brasiliense, detached from stems of Thai rice. Their structures were determined by extensive spectroscopic methods. Mollicellins X, H, and F (3, 8 and 10) showed potent cytotoxicity against the human oral epidermoid carcinoma (KB) cell line, and mollicellin F (10) also showed a potent cytotoxicity against the human hepatocellular carcinoma (HepG2) cell line. Besides, mollicellin B (11) exhibited cytotoxicity against the colorectal adenocarcinoma (HT-29) cell line. Moreover, most of the isolated depsidones displayed potent antibacterial activity against Gram-positive bacteria, Bacillus cereus and Bacillus subtilis, and several of them showed moderate activity against Methicillin-resistant Staphylococcus aureus (MRSA) and clinical isolates of S. aureus. In addition, a few of them also showed moderate activity against a Gram-negative bacteria Pseudomonas aeruginosa.
- MeSH
- antibakteriální látky chemie MeSH
- antitumorózní látky * chemie MeSH
- Chaetomium * chemie MeSH
- depsidy MeSH
- laktony MeSH
- lidé MeSH
- methicilin rezistentní Staphylococcus aureus * MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- rýže (rod) * MeSH
- Sordariales MeSH
- Staphylococcus aureus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Thajsko MeSH
