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1.
Protein Pept Lett ; 31(5): e040724231578, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38967080

RESUMEN

BACKGROUND: Staphylococcus aureus is a common pathogen with strains that are resistant to existing antibiotics. MurJ from S. aureus (SaMurJ), an integral membrane protein functioning as Lipid II flippase, is a potential target for developing new antibacterial agents against this pathogen. Successful expression and purification of this protein shall be useful in the development of drugs against this target. OBJECTIVE: In this study, we demonstrated the optimized expression and purification procedures of SaMurJ, identified suitable detergent for extracting and solubilizing the protein, and examined the peptidisc system to generate a detergent-free environment. METHODS: SaMurJ fused with N-terminal ten-His tag was expressed without induction. Six detergents were selected for screening the most efficient candidate for extraction and solubilization of the protein. The thermostability of the detergent-solubilized protein was assessed by evaluated temperature incubation. Different ratios of peptidisc bi-helical peptide (NSPr) to SaMurJ were mixed and the on-bead peptidisc assembly method was applied. RESULTS: SaMurJ expressed in BL21(DE3) was confirmed by peptide fingerprinting, with a yield of 1 mg SaMurJ per liter culture. DDM was identified as the optimum detergent for solubilization and the nickel affinity column enabled SaMurJ purification with a purity of ~88%. However, NSPr could not stabilize SaMurJ. CONCLUSION: The expression and purification of SaMurJ were successful, with high purity and good yield. SaMurJ can be solubilized and stabilized by a DDM-containing buffer.


Asunto(s)
Proteínas Bacterianas , Staphylococcus aureus , Staphylococcus aureus/enzimología , Staphylococcus aureus/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/química , Proteínas Bacterianas/aislamiento & purificación , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/metabolismo , Detergentes/química , Escherichia coli/genética , Escherichia coli/metabolismo , Solubilidad , Expresión Génica , Uridina Difosfato Ácido N-Acetilmurámico/análogos & derivados
2.
Sci Rep ; 14(1): 15441, 2024 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965246

RESUMEN

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9-23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds. All the synthesized compounds were tested as antimicrobial agents against some clinically bacterial pathogens such as Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compounds 15, 16, 17, 19 and 22 showed potent antimicrobial activity with promising MIC values compared to the positive controls. Moreover, compounds 15 and 22 provide a potent lipid peroxidation (LPO) of the bacterial cell wall. On the other hand, we investigated the anti-proliferative activity of compounds 9-23 against selected human cancerous cell lines of breast (MCF-7), colon (HCT-116), and lung (A549) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and pro-apoptotic protein markers. The results of MTT assay revealed that compounds 10, 13, 21, 22 and 23 possessed highly cytotoxic effects. Out of these, three synthesized compounds 13, 21 and 22 showed cytotoxicity with IC50 values (13, IC50 = 62.4 ± 0.128 and 22, IC50 = 91.6 ± 0.112 µM, respectively, on MCF-7), (13, IC50 = 43.5 ± 0.15 and 21, IC50 = 38.5 ± 0.17 µM, respectively, on HCT-116). Cell cycle and apoptosis/necrosis assays demonstrated that compounds 13 and 22 induced S and G2/M phase cell cycle arrest in MCF-7 cells, while only compound 13 had this effect on HCT-116 cells. Furthermore, compound 13 exhibited the greatest potency in inducing apoptosis in both cell lines compared to compounds 21 and 22. Docking studies indicated that compounds 10, 13, 21 and 23 could potentially inhibit enzymes and exert promising antimicrobial effects, as evidenced by their lower binding energies and various types of interactions observed at the active sites of key enzymes such as Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of K. pneumenia and Gyrase B of B. subtilis. Moreover, 13, 21, and 22 demonstrated minimal binding energy and favorable affinity towards the active pocket of anticancer receptor proteins, including CDK2, EGFR, Erα, Topoisomerase II and VEGFFR. Physicochemical properties, drug-likeness, and ADME (absorption, distribution, metabolism, excretion, and toxicity) parameters of the selected compounds were also computed.


Asunto(s)
Antiinfecciosos , Antineoplásicos , Pruebas de Sensibilidad Microbiana , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antiinfecciosos/farmacología , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Tecnología Química Verde/métodos , Proliferación Celular/efectos de los fármacos , Candida albicans/efectos de los fármacos , Simulación del Acoplamiento Molecular , Células MCF-7 , Antibacterianos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Bacterias/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos
3.
Biol Pharm Bull ; 47(7): 1321-1325, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39019612

RESUMEN

Pyrogens, classified as bacterial endotoxins and non-endotoxin pyrogens (NEPs), induce fever or shock when released into the bloodstream or spinal fluid. Recently, a monocyte-activation test (MAT) involving human cell culture has been developed to detect pyrogens in injectable products. To evaluate the sensitivity of MAT, a reference standard endotoxin was used as a positive control; however, the reactivity differed between the endotoxins and NEPs, necessitating positive controls for NEPs. This study aimed to explore a preparation method for heat-killed Staphylococcus aureus (HKSA) as a positive control for NEPs in MAT. Because S. aureus forms grape-like clusters, nine types of glass filters with pore sizes of 0.5-2.7 µm were evaluated to obtain a uniform bacterial suspension. The suspension was then heat-treated to kill the bacteria, resulting in HKSA samples. Serial dilutions of HKSA were tested by MAT using peripheral blood mononuclear cells. The interleukin-6 concentrations in the culture supernatant were measured by enzyme-linked immuno-sorbent assay to assess pyrogenic activities of HKSA. The pore sizes of the glass filters affected the uniformity of HKSA, and GF/C filter was selected for HKSA preparation. Repeated filtration improved uniformity, and a uniform suspension of HKSA was obtained through double filtration using a GF/C filter. Despite the decrease in HKSA activity as filtration frequency increased, the detection limit remained consistently unchanged. This suggests that repeated filtration can adjust the activity of HKSA to a baseline level and that a uniform suspension of HKSA exhibiting low variation is suitable as a positive control in MAT.


Asunto(s)
Calor , Monocitos , Pirógenos , Staphylococcus aureus , Humanos , Monocitos/inmunología , Interleucina-6/metabolismo , Leucocitos Mononucleares/inmunología , Filtración , Suspensiones
4.
J Nanobiotechnology ; 22(1): 414, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39010059

RESUMEN

Staphylococcus aureus (SA) poses a serious risk to human and animal health, necessitating a low-cost and high-performance analytical platform for point-of-care diagnostics. Cellulose paper-based field-effect transistors (FETs) with RNA-cleaving DNAzymes (RCDs) can fulfill the low-cost requirements, however, its high hydrophilicity and lipophilicity hinder biochemical modification and result in low sensitivity, poor mechanical stability and poor fouling performance. Herein, we proposed a controllable self-cleaning FET to simplify biochemical modification and improve mechanical stability and antifouling performance. Then, we constructed an RCD-based DNA nanotree to significantly enhance the sensitivity for SA detection. For controllable self-cleaning FET, 1 H,1 H,2 H,2 H-perfluorodecyltrimethoxysilane based-polymeric nanoparticles were synthesized to decorate cellulose paper and whole carbon nanofilm wires. O2 plasma was applied to regulate to reduce fluorocarbon chain density, and then control the hydrophobic-oleophobic property in sensitive areas. Because negatively charged DNA affected the sensitivity of semiconducting FETs, three Y-shaped branches with low-cost were designed and applied to synthesize an RCD-based DNA-Nanotree based on similar DNA-origami technology, which further improved the sensitivity. The trunk of DNA-Nanotree was composed of RCD, and the canopy was self-assembled using multiple Y-shaped branches. The controllable self-cleaning FET biosensor was applied for SA detection without cultivation, which had a wide linear range from 1 to 105 CFU/mL and could detect a low value of 1 CFU/mL.


Asunto(s)
Técnicas Biosensibles , ADN Catalítico , Staphylococcus aureus , ADN Catalítico/química , ADN Catalítico/metabolismo , Técnicas Biosensibles/métodos , Transistores Electrónicos , ARN/metabolismo , Límite de Detección , Celulosa/química , Papel , Nanopartículas/química , Humanos
5.
ACS Appl Mater Interfaces ; 16(28): 37041-37051, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38950151

RESUMEN

Slide-ring hydrogels containing polyrotaxane structures have been widely developed, but current methods are more complex, in which modified cyclodextrins, capped polyrotaxanes, and multistep reactions are often needed. Here, a simple one-pot method dissolving the pseudopolyrotaxane (pPRX) in a mixture of acrylamide and boric acid to form a slide-ring hydrogel by UV light is used to construct a tough, puncture-resistant antibacterial polyrotaxane hydrogel. As a new dynamic ring cross-linking agent, boric acid effectively improves the mechanical properties of the hydrogel and involves the hydrogel with fracture toughness. The polyrotaxane hydrogel can withstand 1 MPa compression stress and maintain the morphology integrity, showing 197.5 mJ puncture energy under a sharp steel needle puncture. Meanwhile, its significant antibacterial properties endow the hydrogel with potential applications in the biomedical field.


Asunto(s)
Antibacterianos , Ciclodextrinas , Escherichia coli , Hidrogeles , Poloxámero , Rotaxanos , Rotaxanos/química , Rotaxanos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Poloxámero/química , Escherichia coli/efectos de los fármacos , Ciclodextrinas/química , Ácidos Bóricos/química , Ácidos Bóricos/farmacología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos
6.
ACS Appl Mater Interfaces ; 16(28): 36117-36130, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38950522

RESUMEN

Better infection control will accelerate wound healing and alleviate associated healthcare burdens. Traditional antibacterial dressings often inadequately control infections, inadvertently promoting antibacterial resistance. Our research unveils a novel, dual-functional living dressing that autonomously generates antibacterial agents and delivers electrical stimulation, harnessing the power of spore-forming Bacillus subtilis. This dressing is built on an innovative wearable microbial fuel cell (MFC) framework, using B. subtilis endospores as a powerful, dormant biocatalyst. The endospores are resilient, reactivating in nutrient-rich wound exudate to produce electricity and antibacterial compounds. The combination allows B. subtilis to outcompete pathogens for food and other resources, thus fighting infections. The strategy is enhanced by the extracellular synthesis of tin oxide and copper oxide nanoparticles on the endospore surface, boosting antibacterial action, and electrical stimulation. Moreover, the MFC framework introduces a pioneering dressing design featuring a conductive hydrogel embedded within a paper-based substrate. The arrangement ensures cell stability and sustains a healing-friendly moist environment. Our approach has proven very effective against three key pathogens in biofilms: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus demonstrating exceptional capabilities in both in vitro and ex vivo models. Our innovation marks a significant leap forward in wearable MFC-based wound care, offering a potent solution for treating infected wounds.


Asunto(s)
Antibacterianos , Bacillus subtilis , Fuentes de Energía Bioeléctrica , Biopelículas , Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , Infección de Heridas , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos , Humanos , Pseudomonas aeruginosa/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Bacillus subtilis/efectos de los fármacos , Biopelículas/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Dispositivos Electrónicos Vestibles , Vendajes , Cobre/química , Cobre/farmacología , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Hidrogeles/farmacología
7.
Lett Appl Microbiol ; 77(7)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38970380

RESUMEN

Alternative strategies for controlling Staphylococcus aureus and other pathogens have been continuously investigated, with nisin, a bacteriocin widely used in the food industry as a biopreservative, gaining increasing attention. In addition to its antimicrobial properties, bacteriocins have significant effects on genome functionality even at inhibitory concentrations. This study investigated the impact of subinhibitory concentrations of nisin on S. aureus. Culturing in the presence of 0.625 µmol l-1 nisin, led to the increased relative expression of hla, saeR, and sarA, genes associated with virulence while expression of the sea gene, encoding staphylococcal enterotoxin A (SEA), decreased. In an in vivo experiment, Galleria mellonella larvae inoculated with S. aureus cultured in the presence of nisin exhibited 97% mortality at 72 h post-infection, compared to over 40% of larvae mortality in larvae infected with S. aureus. A comprehensive understanding of the effect of nisin on the transcriptional response of virulence genes and the impact of these changes on the virulence of S. aureus can contribute to assessing the application of this bacteriocin in food and medical contexts.


Asunto(s)
Antibacterianos , Larva , Mariposas Nocturnas , Nisina , Staphylococcus aureus , Nisina/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidad , Animales , Virulencia/genética , Larva/microbiología , Larva/efectos de los fármacos , Antibacterianos/farmacología , Mariposas Nocturnas/microbiología , Infecciones Estafilocócicas/microbiología , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Factores de Virulencia/genética , Pruebas de Sensibilidad Microbiana
8.
ACS Appl Mater Interfaces ; 16(28): 36017-36029, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38975983

RESUMEN

Oral infectious diseases have a significant impact on the health of oral and maxillofacial regions, as well as the overall well-being of individuals. Carvacrol and thymol, two isomers known for their effective antibacterial and anti-inflammatory properties, have gained considerable attention in the treatment of oral infectious diseases. However, their application as topical drugs for oral use is limited due to their poor physical and chemical stability. UiO-66, a metal-organic framework based on zirconium ion (Zr4+), exhibits high drug loading capability. Carvacrol and thymol were efficiently loaded onto UiO-66 with loading rates of 79.60 ± 0.71% and 79.65 ± 0.76%, respectively. The release rates of carvacrol and thymol were 77.82 ± 0.87% and 76.51 ± 0.58%, respectively, after a period of 72 h. Moreover, Car@UiO-66 and Thy@UiO-66 demonstrated excellent antibacterial properties against Candida albicans, Escherichia coli, and Staphylococcus aureus with minimum bactericidal concentrations (MBC) of 0.313 mg/mL, 0.313 mg/mL, and 1.25 mg/mL, respectively. Furthermore, based on the results of the CCK8 cytotoxicity assay, even at concentrations as high as 1.25 mg/mL, Car@UiO-66 and Thy@UiO-66 exhibited excellent biocompatibility with a relative cell survival rate above 50%. These findings suggest that Car@UiO-66 and Thy@UiO-66 possess favorable biocompatibility properties without significant toxicity towards periodontal membrane cells. Additionally, in vivo studies confirmed the efficacy of Car@UiO-66and Thy@UiO-66 in reducing inflammation, promoting bone formation through inhibition of TNF-a and IL6 expression, enhancement of IL10 expression, and acceleration of bone defect healing. Therefore, the unique combination of antibacterial, anti-inflammatory, and osteogenic properties make Car@UiO-66 and Thy@Ui O-66 promising candidates for the treatment of oral infectious diseases and repairing bone defects.


Asunto(s)
Antibacterianos , Antiinflamatorios , Candida albicans , Cimenos , Escherichia coli , Estructuras Metalorgánicas , Staphylococcus aureus , Timol , Timol/química , Timol/farmacología , Cimenos/química , Cimenos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Candida albicans/efectos de los fármacos , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Pruebas de Sensibilidad Microbiana , Ratas , Osteogénesis/efectos de los fármacos , Humanos
9.
Int J Mol Sci ; 25(13)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-39000557

RESUMEN

The effects of intestinal microflora on extraintestinal immune response by intestinal cytokines and metabolites have been documented, but whether intestinal microbes stimulate serum antibody generation is unknown. Here, serum antibodies against 69 outer membrane proteins of Escherichia coli, a dominant bacterium in the human intestine, are detected in 141 healthy individuals of varying ages. Antibodies against E. coli outer membrane proteins are determined in all serum samples tested, and frequencies of antibodies to five outer membrane proteins (OmpA, OmpX, TsX, HlpA, and FepA) are close to 100%. Serum antibodies against E. coli outer membrane proteins are further validated by Western blot and bacterial pull-down. Moreover, the present study shows that OstA, HlpA, Tsx, NlpB, OmpC, YfcU, and OmpA provide specific immune protection against pathogenic E. coli, while HlpA and OmpA also exhibit cross-protection against Staphylococcus aureus infection. These finding indicate that intestinal E. coli activate extraintestinal antibody responses and provide anti-infective immunity.


Asunto(s)
Anticuerpos Antibacterianos , Proteínas de la Membrana Bacteriana Externa , Escherichia coli , Humanos , Escherichia coli/inmunología , Anticuerpos Antibacterianos/inmunología , Anticuerpos Antibacterianos/sangre , Proteínas de la Membrana Bacteriana Externa/inmunología , Adulto , Femenino , Staphylococcus aureus/inmunología , Masculino , Formación de Anticuerpos/inmunología , Persona de Mediana Edad , Proteínas de Escherichia coli/inmunología , Adulto Joven , Anciano , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Adolescente , Infecciones por Escherichia coli/inmunología , Infecciones por Escherichia coli/microbiología
10.
Int J Mol Sci ; 25(13)2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-39000566

RESUMEN

Staphylococcal toxic shock syndrome (STSS) is a rare, yet potentially fatal disease caused by Staphylococcus aureus (S. aureus) enterotoxins, known as superantigens, which trigger an intense immune response. Our previous study demonstrated the protective effect of tofacitinib against murine toxin-induced shock and a beneficial effect against S. aureus sepsis. In the current study, we examined the effects of tofacitinib on T-cell response in peripheral blood using a mouse model of enterotoxin-induced shock. Our data revealed that tofacitinib suppresses the activation of both CD4+ and CD8+ T cells in peripheral blood. Furthermore, both gene and protein levels of Th1 cytokines were downregulated by tofacitinib treatment in mice with enterotoxin-induced shock. Importantly, we demonstrated that CD4+ cells, but not CD8+ cells, are pathogenic in mice with enterotoxin-induced shock. In conclusion, our findings suggest that tofacitinib treatment suppresses CD4+ T-cell activation and Th1 response, thereby aiding in protection against staphylococcal toxic shock in mice. This insight may guide the future development of novel therapies for STSS.


Asunto(s)
Linfocitos T CD4-Positivos , Activación de Linfocitos , Piperidinas , Pirimidinas , Choque Séptico , Infecciones Estafilocócicas , Células TH1 , Animales , Piperidinas/farmacología , Piperidinas/uso terapéutico , Células TH1/inmunología , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Pirimidinas/farmacología , Pirimidinas/uso terapéutico , Choque Séptico/tratamiento farmacológico , Choque Séptico/inmunología , Choque Séptico/inducido químicamente , Ratones , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Activación de Linfocitos/efectos de los fármacos , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Enterotoxinas , Staphylococcus aureus/efectos de los fármacos , Citocinas/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Ratones Endogámicos C57BL , Femenino , Modelos Animales de Enfermedad , Superantígenos/inmunología
11.
Luminescence ; 39(7): e4829, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39004775

RESUMEN

A ratio luminescence probe was developed for detecting Staphylococcus aureus (S. aureus) based on luminescence energy transfer (LET) using double-wavelength emission (550 nm and 812 nm) upconversion nanoparticles (UCNPs) as donor, gold nanoparticles (AuNPs) as acceptor and the aptamer for S. aureus as the specific recognition and link unit. The LET process could cause luminescence quenching because of the spectral overlap between the acceptor and the donor at 550 nm. In the presence of S. aureus, S. aureus selectively combined with the aptamer, and the AuNPs left the surface of UCNPs, which weakened the quenching effect and restored the luminescence of UCNPs. Based on this, the ratio detection was realized by monitoring the change of the luminescence signal of the probe at 550 nm and taking the luminescence signal at 812 nm as the reference signal. Crucially, the probe has a fast reaction speed, with a reaction time of 25 min, and the detection of S. aureus is realized in the concentration range of 5.0 × 103-3.0 × 105 CFU/ml, with the detection limit of 106 CFU/ml. Therefore, the ratio probe has great potential for detecting of S. aureus in food because of its high sensitivity, fast speed and good selectivity.


Asunto(s)
Aptámeros de Nucleótidos , Transferencia de Energía , Oro , Luminiscencia , Mediciones Luminiscentes , Nanopartículas del Metal , Staphylococcus aureus , Staphylococcus aureus/aislamiento & purificación , Oro/química , Nanopartículas del Metal/química , Aptámeros de Nucleótidos/química , Límite de Detección
12.
Arch Microbiol ; 206(8): 350, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38995446

RESUMEN

KKL-35 is a new oxadiazole compound with potent broad-spectrum antibacterial activity against a number of gram-positive and gram-negative bacteria. However, its influences on bacterial growth are unclear. This study is to investigate phenotypic changes of Staphylococcus aureus (SA) caused by KKL-35 and evaluate antibacterial activity of combinations of KKL-35 with 7 class of antibiotics available in medical facilities. KKL-35-treated SA showed significantly lower survival under stresses of NaCl and H2O2 than DMSO (21.03 ± 2.60% vs. 68.21 ± 5.31% for NaCl, 4.91 ± 3.14% vs. 74.78 ± 2.88% for H2O2). UV exposure significantly decreased survival of SA treated with KKL-35 than DMSO-treated ones (23.91 ± 0.71% vs. 55.45 ± 4.70% for 4.2 J/m2, 12.80 ± 1.03% vs. 31.99 ± 5.99% for 7.0 J/m2, 1.52 ± 0.63% vs. 6.49 ± 0.51% for 14.0 J/m2). KKL-35 significantly decreased biofilm formation (0.47 ± 0.12 vs. 1.45 ± 0.21) and bacterial survival in the serum resistance assay (42.27 ± 2.77% vs. 78.31 ± 5.64%) than DMSO. KKL-35 significantly decreased ethidium bromide uptake and efflux, as well as the cell membrane integrity. KKL-35 had low cytotoxicity and low propensity for resistance. KKL-35 inhibited SA growth in concentration-independent and time-dependent manners, and showed additivity when combined with the majority class of available antibiotics. Antibiotic combinations of KKL-35 with ciprofloxacin, rifampicin, or linezolid significantly decreased bacterial loads than the most active antibiotic in the corresponding combination. Thus, KKL-35 inhibits growth of SA by decreasing bacterial environmental adaptations, biofilm formation, membrane uptake and efflux, as well as increasing antibiotic sensitivity. Its potent antibacterial activity, low cytotoxicity, low propensity for resistance, and wide choices in antibiotic combinations make KKL-35 a promising leading compound to design new antibiotics in monotherapies and combination therapies to treat bacterial infections.


Asunto(s)
Antibacterianos , Biopelículas , Pruebas de Sensibilidad Microbiana , Oxadiazoles , Staphylococcus aureus , Humanos , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Oxadiazoles/farmacología , Fenotipo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo
13.
Molecules ; 29(13)2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38998932

RESUMEN

Microbial contamination has profoundly impacted human health, and the effective eradication of widespread microbial issues is essential for addressing serious hygiene concerns. Taking polystyrene (PS) membrane as an example, we herein developed report a robust strategy for the in situ preparation of chlorine-regenerable antimicrobial polymer molecular sieve membranes through combining post-crosslinking and nucleophilic substitution reaction. The cross-linking PS membranes underwent a reaction with 5,5-dimethylhydantoin (DMH), leading to the formation of polymeric N-halamine precursors (PS-DMH). These hydantoinyl groups within PS-DMH were then efficiently converted into biocidal N-halamine structures (PS-DMH-Cl) via a simple chlorination process. ATR-FTIR and XPS spectra were recorded to confirm the chemical composition of the as-prepared PS-DMH-Cl membranes. SEM analyses revealed that the chlorinated PS-DMH-Cl membranes displayed a rough surface with a multitude of humps. The effect of chlorination temperature and time on the oxidative chlorine content in the PS-DMH-Cl membranes was systematically studied. The antimicrobial assays demonstrated that the PS-DMH-Cl membranes could achieve a 6-log inactivation of E. coli and S. aureus within just 4 min of contact time. Additionally, the resulting PS-DMH-Cl membranes exhibited excellent stability and regenerability of the oxidative chlorine content.


Asunto(s)
Cloro , Escherichia coli , Membranas Artificiales , Staphylococcus aureus , Cloro/química , Escherichia coli/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Halogenación , Polímeros/química , Poliestirenos/química , Hidantoínas/química , Hidantoínas/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Aminas
14.
Molecules ; 29(13)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38998969

RESUMEN

In this study, the isolation of compounds from the aerial parts of Morina persica L. and the antimicrobial, antioxidant and antityrosinase activities of various polarity extracts and isolated compounds were investigated. Column chromatography methods were used for isolation. A microdilution method was used to determine antimicrobial activity; Folin-Ciocalteu method was used to determine total phenolic content; DPPH and ABTS radical scavenging- capacity methods were used to determine antioxidant activity; and a mushroom tyrosinase method was used to determine antityrosinase activity. Kaempferol-3-O-ß-glucopyranoside (astragalin) and quercetin-3-O-rutinoside (rutin) were isolated from M. persica. The extracts and compounds showed higher activity against Staphylococcus aureus and Enterococcus faecalis than other tested bacteria. The highest phenolic content, DPPH, and ABTS radical scavenging activity were detected in an ethyl acetate extract at 50 µg/mL concentration. The methanol extract showed the highest antityrosinase effect at 200 µg/mL concentration.


Asunto(s)
Antiinfecciosos , Antioxidantes , Extractos Vegetales , Antioxidantes/farmacología , Antioxidantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Pruebas de Sensibilidad Microbiana , Fenoles/farmacología , Fenoles/química , Fenoles/análisis , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/química , Staphylococcus aureus/efectos de los fármacos
15.
Molecules ; 29(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38999050

RESUMEN

Recently, nanoparticles have received considerable attention owing to their efficiency in overcoming the limitations of traditional chemotherapeutic drugs. In our study, we synthesized a vanillic acid nanocomposite using both chitosan and silver nanoparticles, tested its efficacy against lung cancer cells, and analyzed its antimicrobial effects. We used several characterization techniques such as ultraviolet-visible spectroscopy (UV-Vis), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDAX), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) to determine the stability, morphological characteristics, and properties of the biosynthesized vanillic acid nanocomposites. Furthermore, the vanillic acid nanocomposites were tested for their antimicrobial effects against Escherichia coli and Staphylococcus aureus, and Candida albicans. The data showed that the nanocomposite effectively inhibited microbes, but its efficacy was less than that of the individual silver and chitosan nanoparticles. Moreover, the vanillic acid nanocomposite exhibited anticancer effects by increasing the expression of pro-apoptotic proteins (BAX, Casp3, Casp7, cyt C, and p53) and decreasing the gene expression of Bcl-2. Overall, vanillic acid nanocomposites possess promising potential against microbes, exhibit anticancer effects, and can be effectively used for treating diseases such as cancers and infectious diseases.


Asunto(s)
Antiinfecciosos , Antineoplásicos , Nanocompuestos , Ácido Vanílico , Ácido Vanílico/química , Ácido Vanílico/farmacología , Nanocompuestos/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/síntesis química , Plata/química , Plata/farmacología , Quitosano/química , Quitosano/farmacología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Candida albicans/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Nanopartículas del Metal/química , Línea Celular Tumoral
16.
Molecules ; 29(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38999084

RESUMEN

Sensitively detecting hazardous and suspected bioaerosols is crucial for safeguarding public health. The potential impact of pollen on identifying bacterial species through fluorescence spectra should not be overlooked. Before the analysis, the spectrum underwent preprocessing steps, including normalization, multivariate scattering correction, and Savitzky-Golay smoothing. Additionally, the spectrum was transformed using difference, standard normal variable, and fast Fourier transform techniques. A random forest algorithm was employed for the classification and identification of 31 different types of samples. The fast Fourier transform improved the classification accuracy of the sample excitation-emission matrix fluorescence spectrum data by 9.2%, resulting in an accuracy of 89.24%. The harmful substances, including Staphylococcus aureus, ricin, beta-bungarotoxin, and Staphylococcal enterotoxin B, were clearly distinguished. The spectral data transformation and classification algorithm effectively eliminated the interference of pollen on other components. Furthermore, a classification and recognition model based on spectral feature transformation was established, demonstrating excellent application potential in detecting hazardous substances and protecting public health. This study provided a solid foundation for the application of rapid detection methods for harmful bioaerosols.


Asunto(s)
Algoritmos , Polen , Espectrometría de Fluorescencia , Staphylococcus aureus , Polen/química , Espectrometría de Fluorescencia/métodos , Staphylococcus aureus/clasificación , Staphylococcus aureus/aislamiento & purificación , Sustancias Peligrosas/análisis , Sustancias Peligrosas/clasificación , Enterotoxinas/análisis , Ricina/análisis , Aerosoles/análisis , Análisis de Fourier
17.
Molecules ; 29(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38999106

RESUMEN

The results of this study showed that the compounds synthesized by the authors have significant potential due to their antibacterial and cytotoxic properties. The apparent antibacterial activity demonstrated by the compounds suggests that they are active antimicrobial agents against common microbial pathogens that cause various socially significant infectious diseases. Compound 6 showed pronounced antimicrobial activity against the Gram-positive test strain Staphylococcus aureus ATCC 6538, and compound 7 demonstrated pronounced antimicrobial activity against the Gram-negative test strain Escherichia coli ATCC 25922 (MIC = 6.3 µg/mL). This allowed us to consider these compounds to have great potential.


Asunto(s)
Antibacterianos , Escherichia coli , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Triazoles , Triazoles/química , Triazoles/farmacología , Triazoles/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Humanos , Estructura Molecular , Relación Estructura-Actividad
18.
Protein Sci ; 33(8): e5088, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38988311

RESUMEN

Antibiotic resistance is recognized as an imminent and growing global health threat. New antimicrobial drugs are urgently needed due to the decreasing effectiveness of conventional small-molecule antibiotics. Antimicrobial peptides (AMPs), a class of host defense peptides, are emerging as promising candidates to address this need. The potential sequence space of amino acids is combinatorially vast, making it possible to extend the current arsenal of antimicrobial agents with a practically infinite number of new peptide-based candidates. However, mining naturally occurring AMPs, whether directly by wet lab screening methods or aided by bioinformatics prediction tools, has its theoretical limit regarding the number of samples or genomic/transcriptomic resources researchers have access to. Further, manually designing novel synthetic AMPs requires prior field knowledge, restricting its throughput. In silico sequence generation methods are gaining interest as a high-throughput solution to the problem. Here, we introduce AMPd-Up, a recurrent neural network based tool for de novo AMP design, and demonstrate its utility over existing methods. Validation of candidates designed by AMPd-Up through antimicrobial susceptibility testing revealed that 40 of the 58 generated sequences possessed antimicrobial activity against Escherichia coli and/or Staphylococcus aureus. These results illustrate that AMPd-Up can be used to design novel synthetic AMPs with potent activities.


Asunto(s)
Péptidos Antimicrobianos , Redes Neurales de la Computación , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/síntesis química , Diseño de Fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Staphylococcus aureus/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química
19.
Nat Commun ; 15(1): 5626, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992046

RESUMEN

As bacteriophages continue to gain regulatory approval for personalized human therapy against antibiotic-resistant infections, there is a need for transformative technologies for rapid target identification through multiple, large, decentralized therapeutic phages biobanks. Here, we design a high throughput phage screening platform comprised of a portable library of individual shelf-stable, ready-to-use phages, in all-inclusive solid tablets. Each tablet encapsulates one phage along with luciferin and luciferase enzyme stabilized in a sugar matrix comprised of pullulan and trehalose capable of directly detecting phage-mediated adenosine triphosphate (ATP) release through ATP bioluminescence reaction upon bacterial cell burst. The tablet composition also enhances desiccation tolerance of all components, which should allow easier and cheaper international transportation of phages and as a result, increased accessibility to therapeutic phages. We demonstrate high throughput screening by identifying target phages for select multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Salmonella enterica, Escherichia coli, and Staphylococcus aureus with targets identified within 30-120 min.


Asunto(s)
Bacteriófagos , Escherichia coli , Ensayos Analíticos de Alto Rendimiento , Terapia de Fagos , Medicina de Precisión , Staphylococcus aureus , Humanos , Terapia de Fagos/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Escherichia coli/virología , Escherichia coli/metabolismo , Escherichia coli/genética , Bacteriófagos/genética , Bacteriófagos/fisiología , Staphylococcus aureus/virología , Medicina de Precisión/métodos , Pseudomonas aeruginosa/virología , Adenosina Trifosfato/metabolismo , Salmonella enterica/virología , Farmacorresistencia Bacteriana Múltiple/genética
20.
Sci Rep ; 14(1): 16043, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38992051

RESUMEN

FtsZ is highly conserved among bacteria and plays an essential role in bacterial cell division. The tense conformation of FtsZ bound to GTP assembles into a straight filament via head-to-tail associations, and then the upper subunit of FtsZ hydrolyzes GTP bound to the lower FtsZ subunit. The subunit with GDP bound disassembles accompanied by a conformational change in the subunit from the tense to relaxed conformation. Although crystal structures of FtsZ derived from several bacterial species have been determined, the conformational change from the relaxed to tense conformation has only been observed in Staphylococcus aureus FtsZ (SaFtsZ). Recent cryo-electron microscopy analyses revealed the three-dimensional reconstruction of the protofilament, in which tense molecules assemble via head-to-tail associations. However, the lower resolution of the protofilament suggested that the flexibility of the FtsZ protomers between the relaxed and tense conformations caused them to form in less-strict alignments. Furthermore, this flexibility may also prevent FtsZs other than SaFtsZ from crystalizing in the tense conformation, suggesting that the flexibility of bacterial FtsZs differs. In this study, molecular dynamics simulations were performed using SaFtsZ and Bacillus subtilis FtsZ in several situations, which suggested that different features of the FtsZs affect their conformational stability.


Asunto(s)
Bacillus subtilis , Proteínas Bacterianas , Proteínas del Citoesqueleto , Simulación de Dinámica Molecular , Conformación Proteica , Staphylococcus aureus , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/química , Bacillus subtilis/metabolismo , Bacillus subtilis/química , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Staphylococcus aureus/metabolismo , Staphylococcus aureus/química , Estabilidad Proteica , Guanosina Trifosfato/metabolismo , Guanosina Trifosfato/química
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