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2.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474038

RESUMO

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage, and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA), by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on Gram-positive (Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma-related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotic, carbenicillin (carb), on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of Gram-positive and Gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.


Assuntos
Queimaduras , Doenças Transmissíveis , Infecções Estafilocócicas , Infecção dos Ferimentos , Humanos , Antibacterianos/farmacologia , Carbenicilina/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Biofilmes , Bactérias , Escherichia coli , Inflamação , Testes de Sensibilidade Microbiana
3.
Int J Mol Sci ; 25(5)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38474008

RESUMO

Organic ammonium and phosphonium salts exert excellent antimicrobial effects by interacting lethally with bacterial membranes. Particularly, quaternary ammonium lipids have demonstrated efficiency both as gene vectors and antibacterial agents. Here, aiming at finding new antibacterial devices belonging to both classes, we prepared a water-soluble quaternary ammonium lipid (6) and a phosphonium salt (1) by designing a synthetic path where 1 would be an intermediate to achieve 6. All synthesized compounds were characterized by Fourier-transform infrared spectroscopy and Nuclear Magnetic Resonance. Additionally, potentiometric titrations of NH3+ groups 1 and 6 were performed to further confirm their structure by determining their experimental molecular weight. The antibacterial activities of 1 and 6 were assessed first against a selection of multi-drug-resistant clinical isolates of both Gram-positive and Gram-negative species, observing remarkable antibacterial activity of both compounds against Gram-positive isolates of Enterococcus and Staphylococcus genus. Further investigations on a wider variety of strains of these species confirmed the remarkable antibacterial effects of 1 and 6 (MICs = 4-16 and 4-64 µg/mL, respectively), while 24 h-time-killing experiments carried out with 1 on different S. aureus isolates evidenced a bacteriostatic behavior. Moreover, both compounds 1 and 6, at the lower MIC concentration, did not show significant cytotoxic effects when exposed to HepG2 human hepatic cell lines, paving the way for their potential clinical application.


Assuntos
Compostos de Amônio , Humanos , Compostos de Amônio/farmacologia , Staphylococcus aureus , Compostos de Amônio Quaternário/química , Antibacterianos/farmacologia , Bactérias Gram-Positivas , Bactérias , Cloreto de Sódio/farmacologia , Cloreto de Sódio na Dieta/farmacologia , Lipídeos/farmacologia , Testes de Sensibilidade Microbiana
4.
Int J Mol Sci ; 25(5)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38474151

RESUMO

Extracellular vesicles (EVs) are lipid bilayers derived from cell membranes, released by both eukaryotic cells and bacteria into the extracellular environment. During production, EVs carry proteins, nucleic acids, and various compounds, which are then released. While Gram-positive bacteria were traditionally thought incapable of producing EVs due to their thick peptidoglycan cell walls, recent studies on membrane vesicles (MVs) in Gram-positive bacteria have revealed their significant role in bacterial physiology and disease progression. This review explores the current understanding of MVs in Gram-positive bacteria, including the characterization of their content and functions, as well as their interactions with host and bacterial cells. It offers a fresh perspective to enhance our comprehension of Gram-positive bacterial EVs.


Assuntos
Vesículas Extracelulares , Bactérias Gram-Positivas , Bactérias , Membranas , Membrana Celular , Bicamadas Lipídicas/metabolismo , Vesículas Extracelulares/metabolismo
5.
Molecules ; 29(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38474462

RESUMO

Both geraniol and the products of its transformation, thanks to their beneficial properties, find a variety of applications in cosmetics. Due to their antioxidant and moisturizing properties, these compounds can be added to skin care products such as face creams, lotions, oils, and masks. In addition, these compounds show some antibacterial and antifungal properties, making them suitable for application in skin care products to help fight against bacteria or fungi. This study determined the antimicrobial activity of geraniol and the compounds which were formed during its transformation in relation to selected Gram-positive bacteria, and the preliminary assessment was made whether these compounds can act as ingredients of preparations with potential antimicrobial activity in the treatment of various human diseases (for example diseases of the skin, digestive system, or urinary tract). In addition, this work presents studies on the microbiological purity of cream samples obtained with different contents of geraniol and its transformation products (contents of the tested compounds: 0.5%, 1.5%, 2.5%, 4%, 8%, and 12%). Antibacterial activity tests were performed using the disc diffusion method against Gram-positive cocci, including the reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, and against the clinical strains Staphylococcus aureus MRSA, Staphylococcus epidermidis, Enterococcus faecalis VRE VanB, Enterococcus faecium VRE VanA, and Enterococcus faecium VRE VanB. The most active ingredient against bacteria of the Staphylococcus genus was citral, followed by linalool and then geraniol. During our tests, in the case of bacteria of the Enterococcus genus, citral also showed the highest activity, but linalool, ocimenes, and geraniol showed a slightly lower activity. Moreover, this study examined the microbiological purity of cream samples obtained with various contents of geraniol and its transformation products. In the tests of the microbiological purity of cream samples, no growth of aerobic bacteria and fungi was found, which proves the lack of microbiological contamination of the obtained cosmetic preparations. On this basis, it was assessed that these compounds have preservative properties in the prepared creams. The addition of the analyzed compounds also had influence on the durability of the creams and had no effect on the change in their consistency, did not negatively affect the separation of phases during storage, and even had a positive effect on organoleptic sensations by enriching the smell of the tested samples.


Assuntos
Monoterpenos Acíclicos , Antibacterianos , Enterococcus faecium , Humanos , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana
6.
Bioorg Chem ; 145: 107239, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428282

RESUMO

Antimicrobial resistance (AMR) is a serious global concern and a huge burden on the healthcare system. Antimicrobial peptides (AMPs) are considered as a solution of AMR due to their membrane-lytic and intracellular mode of action and therefore resistance development against AMPs is less frequent. One such AMPs, temporin-L (TL) is a 13-mer peptide reported as a potent and broad-spectrum antibacterial agent with significant immunomodulatory activity. However, TL is toxic to human erythrocytes at their antibacterial concentrations and therefore various analogues were synthesized with potent antimicrobial activity and lower hemolytic activity. In this work, we have selected a non-toxic engineered analogue of TL (eTL) and performed hydrocarbon stapling of amino acid residues at i to i + 4 positions at different part of sequence. The synthesized peptides were investigated against both the gram-positive and gram-negative bacteria as well as methicillin resistant S. aureus, its MIC was measured in the concentrations range of 0.9-15.2 µM. All analogues were found equal or better antibacterial as compared to parent peptide. Interestingly one analogue eTL [5-9] was found to be non-cytotoxic and stable in presence of the human serum. Mode of action studies revealed membrane depolarizing and disruptive mode of action with live MRSA. Further in vivo studies of antimicrobial against MRSA infection and anti-endotoxin activities in mice model revealed potential activity of the stapled peptide analogue. Overall, this reports on stapled analogue of the AMPs highlights an important strategy for the development of new antibacterial therapeutics against AMR.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Animais , Camundongos , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Peptídeo Hidrolases , Bactérias Gram-Positivas , Bactérias Gram-Negativas , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Anti-Infecciosos/farmacologia , Endopeptidases , Hidrocarbonetos , Testes de Sensibilidade Microbiana
7.
Nat Commun ; 15(1): 2007, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38453922

RESUMO

Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.


Assuntos
Neoplasias , Receptores Fc , Camundongos , Animais , Humanos , Imunoglobulina G , Meia-Vida , Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/metabolismo , Camundongos Transgênicos , Anticorpos Monoclonais , Antígenos de Histocompatibilidade Classe I/metabolismo , Neoplasias/terapia , Neoplasias/tratamento farmacológico
8.
ACS Appl Mater Interfaces ; 16(11): 13422-13438, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38442213

RESUMO

Current treatment for chronic infectious wounds is limited due to severe drug resistance in certain bacteria. Therefore, the development of new composite hydrogels with nonantibiotic antibacterial and pro-wound repair is important. Here, we present a photothermal antibacterial composite hydrogel fabricated with a coating of Fe2+ cross-linked carboxymethyl chitosan (FeCMCS) following the incorporation of melanin nanoparticles (MNPs) and the CyRL-QN15 peptide. Various physical and photothermal properties of the hydrogel were characterized. Cell proliferation, migration, cycle, and free-radical scavenging activity were assessed, and the antimicrobial properties of the hydrogel were probed by photothermal therapy. The effects of the hydrogel were validated in a model of methicillin-resistant Staphylococcus aureus (MRSA) infection with full-thickness injury. This effect was further confirmed by changes in cytokines associated with inflammation, re-epithelialization, and angiogenesis on the seventh day after wound formation. The MNPs demonstrated robust photothermal conversion capabilities. The composite hydrogel (MNPs/CyRL-QN15/FeCMCS) promoted keratinocyte and fibroblast proliferation and migration while exhibiting high antibacterial efficacy, effectively killing more than 95% of Gram-positive and Gram-negative bacteria. In vivo study using an MRSA-infected full-thickness injury model demonstrated good therapeutic efficacy of the hydrogel in promoting regeneration and remodeling of chronically infected wounds by alleviating inflammatory response and accelerating re-epithelialization and collagen deposition. The MNPs/CyRL-QN15/FeCMCS hydrogel showed excellent antibacterial and prohealing effects on infected wounds, indicating potential as a promising candidate for wound healing promotion.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Antibacterianos/farmacologia , Hidrogéis/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Melaninas , Peptídeos
9.
Eur J Med Chem ; 268: 116293, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38447461

RESUMO

Global public health is facing a serious problem as a result of the rise in antibiotic resistance and the decline in the discovery of new antibiotics. In this study, two series of amphiphilic-cephalosporins were designed and synthesized, several of which showed good antibacterial activity against both Gram-positive and Gram-negative bacteria. Structure-activity relationships indicated that the length of the hydrophobic alkyl chain significantly affects the antibacterial activity against Gram-negative bacteria. The best compound 2d showed high activity against drug-susceptible Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) with MICs of 0.5 and 2-4 µg/mL, respectively. Furthermore, 2d remained active in complex mammalian body fluids and had a longer post-antibiotic effect (PAE) than vancomycin. Mechanism studies indicated that compound 2d lacks membrane-damaging properties and can target penicillin-binding proteins to disrupt bacterial cell wall structure, inhibit the metabolic activity and induce the accumulation of reactive oxygen species (ROS) in bacteria. Compound 2d showed minimal drug resistance and was nontoxic to HUVEC and HBZY-1 cells with CC50 > 128 µg/mL. These findings suggest that 2d is a promising drug candidate for treating bacterial infections.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/química , Cefalosporinas/farmacologia , Bactérias Gram-Positivas , Bactérias Gram-Negativas , Monobactamas/farmacologia , Testes de Sensibilidade Microbiana , Mamíferos
10.
Eur J Med Chem ; 268: 116303, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38458107

RESUMO

Methionyl-tRNA synthetase (MetRS) catalyzes the attachment of l-methionine (l-Met) to tRNAMet to generate methionyl-tRNAMet, an essential substrate for protein translation within ribosome. Owing to its indispensable biological function and the structural discrepancies with human counterpart, bacterial MetRS is considered an ideal target for developing antibacterials. Herein, chlorhexidine (CHX) was identified as a potent binder of Staphylococcus aureus MetRS (SaMetRS) through an ATP-aided affinity screening. The co-crystal structure showed that CHX simultaneously occupies the enlarged l-Met pocket (EMP) and the auxiliary pocket (AP) of SaMetRS with its two chlorophenyl groups, while its central hexyl linker swings upwards to interact with some conserved hydrophobic residues. ATP adopts alternative conformations in the active site cavity, and forms ionic bonds and water-mediated hydrogen bonds with CHX. Consistent with this synergistic binding mode, ATP concentration-dependently enhanced the binding affinity of CHX to SaMetRS from 10.2 µM (no ATP) to 0.45 µM (1 mM ATP). While it selectively inhibited two representative type 1 MetRSs from S. aureus and Enterococcus faecalis, CHX did not show significant interactions with three tested type 2 MetRSs, including human cytoplasmic MetRS, in the enzyme inhibition and biophysical binding assays, probably due to the conformational differences between two types of MetRSs at their EMP and AP. Our findings on CHX may inspire the design of MetRS-directed antimicrobials in future.


Assuntos
Metionina tRNA Ligase , Humanos , Metionina tRNA Ligase/química , Metionina tRNA Ligase/genética , Metionina tRNA Ligase/metabolismo , Clorexidina/farmacologia , Staphylococcus aureus , RNA de Transferência de Metionina/metabolismo , Bactérias Gram-Positivas/metabolismo , Trifosfato de Adenosina/metabolismo
11.
Lett Appl Microbiol ; 77(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38467396

RESUMO

Endophytic microorganisms associated with medicinal plants are of particular interest as they are a potential source of new bioactive chemicals effective against novel emerging and drug-resistant pathogens. Agave americana is a tropical medicinal plant with antibacterial, antifungal, and anticancer properties. We studied the biodiversity of fungal endophytes of A. americana and their antimicrobial production potential. Isolated endophytic fungi were classified into 32 morphotypes (15 from stem and 17 from leaf) based on their cultural and morphological characteristics. Among the fungal crude extracts tested, 82% of isolates from the leaves and 80% of the isolates from the stem showed antibacterial activity against the bacterial strains (Escherichia coli ATTC 25902, Staphylococcus aureus ATTC 14775, and Bacillus subtilis NRRL 5109) tested. Extracts from four fungal isolates from leaves showed antifungal activity against at least one of the fungal strains (Candida albicans ATTC 10231 and Aspergillus fumigatus NRRL 5109) tested. Crude extracts of seven fungal isolates showed a zone of inhibition of more than 11 mm at 10 mgml-1 against both Gram-positive and Gram-negative bacteria tested. Penicillium, Colletotrichum, Curvularia, Pleosporales, Dothideomycetes, and Pleurotus are the main endophytes responsible for bioactive potential. These results indicate that A. americana harbors endophytes capable of producing antimicrobial metabolites.


Assuntos
Agave , Anti-Infecciosos , Ascomicetos , Plantas Medicinais , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Antibacterianos/farmacologia , Plantas Medicinais/microbiologia , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Bactérias Gram-Positivas , Fungos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/metabolismo , Endófitos , Misturas Complexas/metabolismo , Misturas Complexas/farmacologia
12.
PLoS One ; 19(3): e0300380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38517855

RESUMO

Antimicrobial resistance (AMR) represents an alarming global challenge to public health. Infections caused by multidrug-resistant Staphylococcus aureus (S. aureus) pose an emerging global threat. Therefore, it is crucial to develop novel compounds with promising antimicrobial activity against S. aureus especially those with challenging resistance mechanisms and biofilm formation. Series of bis(thiazol-5-yl)phenylmethane derivatives were evaluated against drug-resistant Gram-positive bacteria. The screening revealed an S. aureus-selective mechanism of bis(thiazol-5-yl)phenylmethane derivatives (MIC 2-64 µg/mL), while significantly lower activity was observed with vancomycin-resistant Enterococcus faecalis (MIC 64 µg/mL) (p<0.05). The most active phenylmethane-based (p-tolyl) derivative, 23a, containing nitro and dimethylamine substituents, and the naphthalene-based derivative, 28b, harboring fluorine and nitro substituents, exhibited strong, near MIC bactericidal activity against S. aureus with genetically defined resistance phenotypes such as MSSA, MRSA, and VRSA and their biofilms. The in silico modeling revealed that most promising compounds 23a and 28b were predicted to bind S. aureus MurC ligase. The 23a and 28b formed bonds with MurC residues at binding site, specifically Ser12 and Arg375, indicating consequential interactions essential for complex stability. The in vitro antimicrobial activity of compound 28b was not affected by the addition of 50% serum. Finally, all tested bis(thiazol-5-yl)phenylmethane derivatives showed favorable cytotoxicity profiles in A549 and THP-1-derived macrophage models. These results demonstrated that bis(thiazol-5-yl)phenylmethane derivatives 23a and 28b could be potentially explored as scaffolds for the development of novel candidates targeting drug-resistant S. aureus. Further studies are also warranted to understand in vivo safety, efficacy, and pharmacological bioavailability of bis(thiazol-5-yl)phenylmethane derivatives.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Infecções Estafilocócicas/microbiologia , Bactérias Gram-Positivas , Testes de Sensibilidade Microbiana
13.
Nat Commun ; 15(1): 2432, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503735

RESUMO

Arrest peptides containing RAPP (ArgAlaProPro) motifs have been discovered in both Gram-positive and Gram-negative bacteria, where they are thought to regulate expression of important protein localization machinery components. Here we determine cryo-EM structures of ribosomes stalled on RAPP arrest motifs in both Bacillus subtilis and Escherichia coli. Together with molecular dynamics simulations, our structures reveal that the RAPP motifs allow full accommodation of the A-site tRNA, but prevent the subsequent peptide bond from forming. Our data support a model where the RAP in the P-site interacts and stabilizes a single hydrogen atom on the Pro-tRNA in the A-site, thereby preventing an optimal geometry for the nucleophilic attack required for peptide bond formation to occur. This mechanism to short circuit the ribosomal peptidyltransferase activity is likely to operate for the majority of other RAPP-like arrest peptides found across diverse bacterial phylogenies.


Assuntos
Peptidil Transferases , Peptidil Transferases/metabolismo , Antibacterianos/metabolismo , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Positivas/genética , Biossíntese de Proteínas , Ribossomos/metabolismo , Peptídeos/metabolismo , RNA de Transferência/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo
14.
Arch Microbiol ; 206(4): 186, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509398

RESUMO

Imidazoles are a category of azole antifungals that encompass compounds such as ketoconazole, miconazole, esomeprazole, and clotrimazole. In contrast, the triazoles group, which includes fluconazole, voriconazole, and itraconazole, also plays a significant role. The rise of antibiotic resistance in fungal pathogens has evolved into a substantial global public health concern. In this study, two newly synthesized imidazo[1,2-a]pyridine derivative (Probe I and Probe II) molecules were investigated for its antimicrobial potency against of a panel of bacterial (Gram-positive and Gram-negative bacteria) and fungal pathogens. Among the different types of pathogens, we found that Probe II showed excellent antifungal activity against fungal pathogens, based on the preliminary screening the potent molecule further investigated against multidrug-resistance Candida sp. (n = 10) and compared with commercial molecules. In addition, in-silico molecular docking, its dynamics, absorption, distribution, metabolism, excretion and toxicity (ADMET) were analyzed. In this study, the small molecule (Probe II) displayed potent activity only against the Candida spp. including several multidrug-resistant Candida spp. Probe II exhibited minimum inhibitory concentration ranges from 4 to 16 µg/mL and minimum fungicidal concentration in the range 4‒32 µg/mL as the lowest concentration enough to eliminate the Candida spp. The selected molecules inhibit the formation of yeast to mold as well as ergosterol formation by the computational simulation against Sterol 14-alpha demethylase (CYP51) and inhibition of ergosterol biosynthesis by in-vitro model show that the Probe II completely inhibits the formation of ergosterol in yeast cells at 2× MIC. The ADMET analysis Probe II could be moderately toxic to the human being, though the in-vitro toxicity studies will help to understand the real-time toxic level. The novel compound Probe II, which was synthesized during the study, shows promise for development into a new generation of drug treatments aimed at addressing the emerging drug resistance in Candida sp.


Assuntos
Candida , Saccharomyces cerevisiae , Humanos , Saccharomyces cerevisiae/metabolismo , Simulação de Acoplamento Molecular , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Fluconazol/farmacologia , Testes de Sensibilidade Microbiana , Ergosterol
15.
J Mater Chem B ; 12(8): 2180-2196, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38323518

RESUMO

In the present work, acidic (direct) and basic precipitation (indirect) methods were used to demonstrate the influence of the mode of precipitation on the structural properties of ZnO nanoparticles (NPs). Four samples of ZnO nanoparticles were prepared, two samples via each mode of precipitation. DZOa and IZOa were the aged samples prepared via acidic and basic precipitation methods, and DZOwa and IZOwa were processed without aging. Both precipitation processes were carried out without using any surfactant reagents. Zinc hydroxide precipitate, which was formed during the basic precipitation method, could be critical in deciding the properties of ZnO NPs, unlike zinc hydroxide formed during acidic precipitation. Aging of zinc hydroxide, synthesised by basic precipitation method for 48 hours was found to be an added advantage in controlling the properties of ZnO NPs. The influence of the mode of precipitation on the structural properties and antibacterial activity of ZnO NPs against Gram-positive and Gram-negative bacterial strains was tested. The antibacterial activity of all four ZnO NPs was analysed via zone of inhibition measurements at a concentration dose of 200 µg ml-1. IZOa nanoparticles prepared using the basic precipitation method showed a higher antibacterial activity against three Gram-negative and one Gram-positive strains, namely, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. DZOa nanoparticles synthesized through acidic precipitation showed relatively high antibacterial activity against Salmonella typhimurium, a Gram-negative strain. ZnO NPs prepared without aging, IZOwa and DZOwa, showed a higher antibacterial activity against E. coli and Bacillus sp. strains, respectively. All ZnO NPs were characterized via UV-visible, FTIR, XRD, and HRSEM techniques.


Assuntos
Hidróxidos , Nanopartículas , Compostos de Zinco , Óxido de Zinco , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Escherichia coli , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias Gram-Positivas
16.
Soft Matter ; 20(9): 2075-2087, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38345756

RESUMO

Salicylic acid (SA) finds extensive applications in the treatment of rheumatic and skin diseases because of its analgesic, anti-inflammatory and exfoliating properties. As it is lipophilic in nature, there is a need for appropriate delivery systems to harness these properties for different applications. Herein, we examined the suitability of Pluronic P123/F127 micellar systems as delivery media by investigating the structural, flow and antimicrobial properties of P123/F127-SA solutions and hydrogels using DLS, SANS, rheological and zone inhibition measurement techniques. SA modulates the aggregation characteristics of these surfactant systems and brings about spherical-to-worm-like micelle-to-vesicular structural transitions in the hydrophobic Pluronic P123 system, a spherical-to-worm-like micellar transition in the mixed P123/F127 system and an onset of inter-micellar attraction in the hydrophilic Pluronic F127 system. SA-solubilized systems of both hydrophobic and hydrophilic Pluronics inhibit the growth of Gram-positive and Gram-negative bacteria with comparable MIC values. This suggests that the interaction of SA molecules with the bacterial cell membrane remains unobstructed upon encapsulation in Pluronic micelles. F127 hydrogel-based SA formulations with rheological properties suitable for topical applications and up to 15% SA loading were prepared. These will be useful SA ointments as F127 is an FDA-approved excipient for topical drug delivery applications. The results indicate that Pluronics remain effective as delivery agents for SA and exhibit interesting structural polymorphism upon its solubilization.


Assuntos
Hidrogéis , Poloxaleno , Poloxâmero , Polietilenos , Polipropilenos , Poloxâmero/química , Ácido Salicílico/farmacologia , Antibacterianos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Micelas
17.
Appl Microbiol Biotechnol ; 108(1): 241, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413482

RESUMO

The present work aimed to develop, characterize, and evaluate the antibacterial and antibiofilm activity of two nanoemulsions (NEs) containing 500 µg/mL of curcumin from Curcuma longa (CUR). These NEs, produced with heating, contain olive oil (5%) and the surfactants tween 80 (5%) and span 80 (2.5%), water q.s. 100 mL, and were stable for 120 days. NE-2-CUR presented Ø of 165.40 ± 2.56 nm, PDI of 0.254, ζ of - 33.20 ± 1.35 mV, pH of 6.49, and Entrapment Drug Efficiency (EE) of 99%. The NE-4-CUR showed a Ø of 105.70 ± 4.13 nm, PDI of 0.459, ζ of - 32.10 ± 1.45 mV, pH of 6.40 and EE of 99.29%. Structural characterization was performed using DRX and FTIR, thermal characterization using DSC and TG, and morphological characterization using SEM, suggesting that there is no significant change in the CUR present in the NEs and that they remain stable. The MIC was performed by the broth microdilution method for nine gram-positive and gram-negative bacteria, as well as Klebsiella pneumoniae clinical isolates resistant to antibiotics and biofilm and efflux pump producers. The NEs mostly showed a bacteriostatic profile. The MIC varied between 125 and 250 µg/mL. The most sensitive bacteria were Staphylococcus aureus and Enterococcus faecalis, for which NE-2-CUR showed a MIC of 125 µg/mL. The NEs and ceftazidime (CAZ) interaction was also evaluated against the K. pneumoniae resistant clinical isolates using the Checkerboard method. NE-2-CUR and NE-4-CUR showed a synergistic or additive profile; there was a reduction in CAZ MICs between 256 times (K26-A2) and 2 times (K29-A2). Furthermore, the NEs inhibited these isolates biofilms formation. The NEs showed a MBIC ranging from 15.625 to 250 µg/mL. Thus, the NEs showed physicochemical characteristics suitable for future clinical trials, enhancing the CAZ antibacterial and antibiofilm activity, thus becoming a promising strategy for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae. KEY POINTS: • The NEs showed physicochemical characteristics suitable for future clinical trials. • The NEs showed a synergistic/additive profile, when associated with ceftazidime. • The NEs inhibited biofilm formation of clinical isolates.


Assuntos
Anti-Infecciosos , Curcumina , Antibacterianos/farmacologia , Ceftazidima/farmacologia , Curcumina/farmacologia , Curcumina/química , Azeite de Oliva/farmacologia , Bactérias Gram-Positivas , Bactérias Gram-Negativas , Anti-Infecciosos/farmacologia , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana
18.
Braz J Biol ; 84: e280487, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38422301

RESUMO

The genus Psidium, belonging to the family Myrtaceae, encompasses several plant species rich in essential oils. Several studies involving different research areas have shown promising results for essential oils, which has attracted interest from diverse sectors, including pharmaceutical, food, and cosmetic industries. Thus, the objective of this study was to evaluate the biological activity of the essential oil extracted from Psidium bahianum leaves (EOPb) collected in an Atlantic Forest remnant in the northern coast of the state of Bahia, Brazil. EOPb was extracted by steam distillation and analyzed through proton nuclear magnetic resonance (1H-NMR). The free radical scavenging activity was assessed using the DPPH methodology (analyzing the scavenging of the stable free radical 1,1-diphenyl-2-picrylhydrazyl). Antimicrobial disk diffusion assays were conducted; toxicity was determined through assays on sheep erythrocytes and Artemia salina. 1H-NMR evaluation showed the presence mainly of monoterpenes and sesquisterpenes. The percentage of antioxidant activity was 18.03±2.53 53 for 125 125 µg mL-1. Antimicrobial assays showed that the essential oil at a concentration of 10 mg mL-1 inhibited the growth of the microorganisms Staphylococcus aureus, Bacillus subtilis, B. cereus, Micrococcus luteus, Escherichia coli, Aspergillus niger, Candida albicans, and C. glabrata. The toxicity results indicated that concentrations of EOPb at 10, 100, 250, and 500 µg mL-1 were not toxic to sheep erythrocytes. The toxicity assay on A. salina showed that the lethal concentration for 50% of individuals (LC50) within 24 and 48 hours were 371.48 and 302 µg mL-1 of EOPb, respectively, which were considered moderately toxic, whereas the LC50 within 72 horas was 33.11 µg mL-1, considered highly toxic. These findings are promising, as the essential oil from P. bahianum leaves showed antimicrobial activity against both Gram-positive and Gram-negative bacteria and fungi. The data obtained for the essential oil toxicity in A. salina could be tested on different tumor cell lines.


Assuntos
Myrtaceae , Óleos Voláteis , Psidium , Humanos , Animais , Ovinos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Antioxidantes/farmacologia , Antioxidantes/química , Radicais Livres , Testes de Sensibilidade Microbiana
19.
J Mater Chem B ; 12(7): 1905-1925, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305576

RESUMO

Hydrogels with multifunctional properties activated at specific times have gained significant attention in the biomedical field. As bacterial infections can cause severe complications that negatively impact wound repair, herein, we present the development of a stimuli-responsive, injectable, and in situ-forming hydrogel with antibacterial, self-healing, and drug-delivery properties. In this study, we prepared a Pluronic F-127 (PF127) and sodium alginate (SA)-based hydrogel that can be targeted to a specific tissue via injection. The PF127/SA hydrogel was incorporated with polymeric short-filaments (SFs) containing an anti-inflammatory drug - ketoprofen, and stimuli-responsive polydopamine (PDA) particles. The hydrogel, after injection, could be in situ gelated at the body temperature, showing great in vitro stability and self-healing ability after 4 h of incubation. The SFs and PDA improved the hydrogel injectability and compressive strength. The introduction of PDA significantly accelerated the KET release under near-infrared light exposure and extended its release validity period. The excellent composites' photo-thermal performance led to antibacterial activity against representative Gram-positive and Gram-negative bacteria, resulting in 99.9% E. coli and S. aureus eradication after 10 min of NIR light irradiation. In vitro, fibroblast L929 cell studies confirmed the materials' biocompatibility and paved the way toward further in vivo and clinical application of the system for chronic wound treatments.


Assuntos
Antibacterianos , Hidrogéis , Antibacterianos/farmacologia , Hidrogéis/farmacologia , Staphylococcus aureus , Escherichia coli , Bactérias Gram-Negativas , Bactérias Gram-Positivas
20.
Sci Rep ; 14(1): 3521, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347115

RESUMO

Nowadays, dermatophyte infections are relatively easy to cure, especially since the introduction of orally administered antifungals such as terbinafine and itraconazole. However, these drugs may cause side effects due to liver damage or their interactions with other therapeutics. Hence, the search for new effective chemotherapeutics showing antidermatophyte activity seems to be the urge of the moment. Potassium salts of N-acylhydrazinecarbodithioates are used commonly as precursors for the synthesis of biologically active compounds. Keeping that in mind, the activity of a series of five potassium N-acylhydrazinecarbodithioates (1a-e) and their aminotriazole-thione derivatives (2a-e) was evaluated against a set of pathogenic, keratinolytic fungi, such as Trichophyton ssp., Microsporum ssp. and Chrysosporium keratinophilum, but also against some Gram-positive and Gram-negative bacteria. All tested compounds were found non-toxic for L-929 and HeLa cells, with the IC30 and IC50 values assessed in the MTT assay above 128 mg/L. The compound 5-amino-3-(naphtalene-1-yl)-4,5-dihydro-1H-1,2,4-triazole-5-thione (2d) was found active against all fungal strains tested. Scanning Electron Microscopy (SEM) revealed inhibition of mycelium development of Trichophyton rubrum cultivated on nail fragments and treated with 2d 24 h after infection with fungal spores. Transmission Electron Microscopy (TEM) observation of mycelium treated with 2d showed ultrastructural changes in the morphology of germinated spores. Finally, the RNA-seq analysis indicated that a broad spectrum of genes responded to stress induced by the 2d compound. In conclusion, the results confirm the potential of N-acylhydrazinecarbodithioate derivatives for future use as promising leads for new antidermatophyte agents development.


Assuntos
Sais , Tionas , Humanos , Amitrol (Herbicida) , Potássio , Antibacterianos/uso terapêutico , Células HeLa , Bactérias Gram-Positivas , Bactérias Gram-Negativas , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Testes de Sensibilidade Microbiana
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