RESUMEN
Bacteria invasion is the main factor hindering the wound-healing process. However, current antibacterial therapies inevitably face complex challenges, such as the abuse of antibiotics or severe inflammation during treatment. Here, a drug-free bioclay enzyme (Bio-Clayzyme) consisting of Fe2+-tannic acid (TA) network-coated kaolinite nanoclay and glucose oxidase (GOx) was reported to destroy harmful bacteria via bimetal antibacterial therapy. At the wound site, Bio-Clayzyme was found to enhance the generation of toxic hydroxyl radicals for sterilization via cascade catalysis of GOx and Fe2+-mediated peroxidase mimetic activity. Specifically, the acidic characteristics of the infection microenvironment accelerated the release of Al3+ from kaolinite, which further led to bacterial membrane damage and amplified the antibacterial toxicity of Fe2+. Besides, Bio-Clayzyme also performed hemostasis and anti-inflammatory functions inherited from Kaol and TA. By the combination of hemostasis and anti-inflammatory and bimetal synergistic sterilization, Bio-Clayzyme achieves efficient healing of infected wounds, providing a revolutionary approach for infectious wound regeneration.
Asunto(s)
Antibacterianos , Glucosa Oxidasa , Cicatrización de Heridas , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/farmacología , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Esterilización/métodos , Arcilla/química , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Hierro/químicaRESUMEN
Wound infections, especially those caused by pathogenic bacteria, present a considerable public health concern due to associated complications and poor therapeutic outcomes. Herein, we developed antibacterial nanoparticles, namely, PGTP, by coordinating guanidine derivatives with a porphyrin-based sonosensitizer. The synthesized PGTP nanoparticles, characterized by their strong positive charge, effectively disrupted the bacterial biosynthesis process through charge interference, demonstrating efficacy against both Gram-negative and Gram-positive bacteria. Additionally, PGTP nanoparticles generated reactive oxygen species under ultrasound stimulation, resulting in the disruption of biofilm integrity and efficient elimination of pathogens. RNA-seq analysis unveiled the detailed mechanism of wound healing, revealing that PGTP nanoparticles, when coupled with ultrasound, impair bacterial metabolism by interfering with the synthesis and transcription of amino acids. This study presents a novel approach to combatting wound infections through ultrasound-driven charge-interfering therapy, facilitated by advanced antibacterial nanomaterials.
Asunto(s)
Antibacterianos , Biopelículas , Nanopartículas , Infección de Heridas , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Nanopartículas/química , Nanopartículas/uso terapéutico , Biopelículas/efectos de los fármacos , Animales , Ratones , Ondas Ultrasónicas , Especies Reactivas de Oxígeno/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Humanos , Porfirinas/química , Porfirinas/farmacología , Porfirinas/uso terapéutico , Terapia por Ultrasonido/métodos , Bacterias Grampositivas/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacosRESUMEN
We report a clinical isolate of Burkholderia thailandensis 2022DZh obtained from a patient with an infected wound in southwest China. Genomic analysis indicates that this isolate clusters with B. thailandensis BPM, a human isolate from Chongqing, China. We recommend enhancing monitoring and surveillance for B. thailandensis infection in both humans and livestock.
Asunto(s)
Infecciones por Burkholderia , Burkholderia , Filogenia , Infección de Heridas , Humanos , Masculino , Burkholderia/genética , Burkholderia/aislamiento & purificación , Burkholderia/clasificación , Infecciones por Burkholderia/microbiología , Infecciones por Burkholderia/diagnóstico , China/epidemiología , Genoma Bacteriano , Infección de Heridas/microbiología , Persona de Mediana EdadRESUMEN
The growing threat of antibiotic-resistant bacterial pathogens necessitates the development of alternative antimicrobial approaches. This is particularly true for chronic wound infections, which commonly harbor biofilm-dwelling bacteria. A novel electrochemical bandage (e-bandage) delivering low-levels of hypochlorous acid (HOCl) was evaluated against Pseudomonas aeruginosa murine wound biofilms. 5 mm skin wounds were created on the dorsum of mice and infected with 106 colony-forming units (CFU) of P. aeruginosa. Biofilms were formed over 2 days, after which e-bandages were placed on the wound beds and covered with Tegaderm. Mice were administered Tegaderm-only (control), non-polarized e-bandage (no HOCl production), or polarized e-bandage (using an HOCl-producing potentiostat), with or without systemic amikacin. Purulence and wound areas were measured before and after treatment. After 48 hours, wounds were harvested for bacterial quantification. Forty-eight hours of polarized e-bandage treatment resulted in mean biofilm reductions of 1.4 log10 CFUs/g (P = 0.0107) vs non-polarized controls and 2.2 log10 CFU/g (P = 0.004) vs Tegaderm-only controls. Amikacin improved CFU reduction in Tegaderm-only (P = 0.0045) and non-polarized control groups (P = 0.0312) but not in the polarized group (P = 0.3876). Compared to the Tegaderm-only group, there was less purulence in the polarized group (P = 0.009). Wound closure was neither impeded nor improved by either polarized or non-polarized e-bandage treatment. Concurrent amikacin did not impact wound closure or purulence. In conclusion, an HOCl-producing e-bandage reduced P. aeruginosa in wound biofilms with no impairment in wound healing, representing a promising antibiotic-free approach for addressing wound infection.
Asunto(s)
Infecciones por Pseudomonas , Infección de Heridas , Animales , Ratones , Pseudomonas aeruginosa , Ácido Hipocloroso , Amicacina , Infecciones por Pseudomonas/microbiología , Infección de Heridas/microbiología , Vendajes , Antibacterianos , BiopelículasRESUMEN
Burn wounds are a major burden, with high mortality rates due to infections. Staphylococcus aureus is a major causative agent of burn wound infections, which can be difficult to treat because of antibiotic resistance and biofilm formation. An alternative to antibiotics is the use of bacteriophages, viruses that infect and kill bacteria. We investigated the efficacy of bacteriophage therapy for burn wound infections, in both a porcine and a newly developed human ex vivo skin model. In both models, the efficacy of a reference antibiotic treatment (fusidic acid) and bacteriophage treatment was determined for a single treatment, successive treatment, and prophylaxis. Both models showed a reduction in bacterial load after a single bacteriophage treatment. Increasing the frequency of bacteriophage treatments increased bacteriophage efficacy in the human ex vivo skin model, but not in the porcine model. In both models, prophylaxis with bacteriophages increased treatment efficacy. In all cases, bacteriophage treatment outperformed fusidic acid treatment. Both models allowed investigation of bacteriophage-bacteria dynamics in burn wounds. Overall, bacteriophage treatment outperformed antibiotic control underlining the potential of bacteriophage therapy for the treatment of burn wound infections, especially when used prophylactically.
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Antibacterianos , Bacteriófagos , Quemaduras , Terapia de Fagos , Infecciones Estafilocócicas , Staphylococcus aureus , Infección de Heridas , Animales , Quemaduras/terapia , Quemaduras/microbiología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/virología , Porcinos , Terapia de Fagos/métodos , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infección de Heridas/terapia , Infección de Heridas/microbiología , Infecciones Estafilocócicas/terapia , Infecciones Estafilocócicas/microbiología , Bacteriófagos/fisiología , Ácido Fusídico/farmacología , Ácido Fusídico/uso terapéutico , Modelos Animales de Enfermedad , Biopelículas/efectos de los fármacos , Piel/microbiologíaRESUMEN
Microorganism are ubiquitous and intimately connected with human health and disease management. The accurate and fast identification of pathogenic microorganisms is especially important for diagnosing infections. Herein, three tetraphenylethylene derivatives (S-TDs: TBN, TPN, and TPI) featuring different cationic groups, charge numbers, emission wavelengths, and hydrophobicities were successfully synthesized. Benefiting from distinct cell wall binding properties, S-TDs were collectively utilized to create a sensor array capable of imaging various microorganisms through their characteristic fluorescent signatures. Furthermore, the interaction mechanism between S-TDs and different microorganisms was explored by calculating the binding energy between S-TDs and cell membrane/wall constituents, including phospholipid bilayer and peptidoglycan. Using a combination of the fluorescence sensor array and a deep learning model of residual network (ResNet), readily differentiation of Gram-negative bacteria (G-), Gram-positive bacteria (G+), fungi, and their mixtures was achieved. Specifically, by extensive training of two ResNet models with large quantities of images data from 14 kinds of microorganism stained with S-TDs, identification of microorganism was achieved at high-level accuracy: over 92.8% for both Gram species and antibiotic-resistant species, with 90.35% accuracy for the detection of mixed microorganism in infected wound. This novel method provides a rapid and accurate method for microbial classification, potentially aiding in the diagnosis and treatment of infectious diseases.
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Aprendizaje Profundo , Humanos , Estilbenos/química , Bacterias Grampositivas/aislamiento & purificación , Colorantes Fluorescentes/química , Bacterias Gramnegativas/aislamiento & purificación , Infección de Heridas/microbiología , Infección de Heridas/diagnóstico , Hongos/aislamiento & purificaciónRESUMEN
A prior analysis suggested that wound swab culture (WSC) results were driving unnecessary antibiotic use in patients who were not already receiving treatment. As a quality-improvement initiative, our laboratory introduced an "exception-reporting" protocol on 1 March 2023, whereby typical wound pathogens susceptible to recommended empiric therapy (flucloxacillin/cefalexin) were not reported, and a comment was provided, stating no significant resistant organisms had been detected. Full results were available to clinicians on request. Cultures falling outside protocol criteria were reported in the standard fashion. This analysis sought to assess the effect of exception-reporting on post-report antibiotic initiation (PRAI). All community WSC results were matched to antibiotic dispensing records from October 2021 to December 2023. Sampling without treatment pre-report was termed "test and wait" (TaW). Following TaW, PRAI was identified if antibiotics were started within 5 days post-report. There were 1,819 and 764 WSCs received in the pre-change and post-change periods, respectively, where an initial TaW approach had been taken and an organism eligible for exception-reporting had been isolated. In the post-change period, 407 (53.3%) met the criteria and were exception-reported. PRAI occurred in 901 (49.5%) pre-change samples, compared to 102 (25.1%, P < 0.01) with exception-reporting. There was no detectable increase in hospitalization or repeat WSC collection in the 30 days following exception-reporting. Exception-reporting was associated with a markedly reduced proportion of patients being initiated on antibiotics following WSC where an organism had been isolated. The naming of organisms in reports appears to drive unnecessary antibiotic prescribing in many patients. These results require confirmation in other jurisdictions. IMPORTANCE: Wound swab culture is a high-volume test performed in clinical microbiology laboratories. In this analysis, we have shown that an alternative approach to reporting positive wound swab cultures has resulted in a large reduction in post-report antibiotic initiation, suggesting that the current standard method of reporting generates considerable unnecessary antibiotic use. If these findings are replicated elsewhere, wider adoption of this reporting would represent an opportunity for many clinical microbiology laboratories to have a significant impact on community antimicrobial stewardship.
Asunto(s)
Antibacterianos , Infección de Heridas , Humanos , Antibacterianos/uso terapéutico , Infección de Heridas/microbiología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/diagnóstico , Femenino , Masculino , Anciano , Persona de Mediana Edad , Adulto , Programas de Optimización del Uso de los Antimicrobianos , Manejo de Especímenes/métodos , Anciano de 80 o más AñosRESUMEN
The use of traditional Ag-based antibacterial agents is usually accompanied by uncontrollable silver release, which makes it difficult to find a balance between antibacterial performance and biosafety. Herein, we prepared a core-shell system of ZIF-8-derived amorphous carbon-coated Ag nanoparticles (Ag@C) as an ideal research model to reveal the synergistic effect and structure-activity relationship of the structural transformation of carbon shell and Ag core on the regulation of silver release behavior. It is found that Ag@C prepared at 600 °C (AC6) exhibits the best ion release kinetics due to the combination of relatively simple shell structure and lower crystallinity of the Ag core, thereby exerting stronger antibacterial properties (>99.999 %) at trace doses (20â µg mL-1) compared with most other Ag-based materials. Meanwhile, the carbon shell prevents the metal Ag from being directly exposed to the organism and thus endows AC6 with excellent biocompatibility. In animal experiments, AC6 can effectively promote wound healing by inactivating drug-resistant bacteria while regulating the expression of TNF-α and CD31. This work provides theoretical support for the scientific design and clinical application of controllable ion-releasing antibacterial agents.
Asunto(s)
Antibacterianos , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Plata , Plata/química , Plata/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Animales , Nanopartículas del Metal/química , Ratones , Cicatrización de Heridas/efectos de los fármacos , Farmacorresistencia Bacteriana/efectos de los fármacos , Carbono/química , Carbono/farmacología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Infección de Heridas/patología , Liberación de Fármacos , Humanos , Staphylococcus aureus/efectos de los fármacosRESUMEN
OBJECTIVES: Pseudomonas aeruginosa and Acinetobacter baumannii are ranked as top-priority organisms by WHO. Antimicrobial peptides (AMPs) are promising antimicrobial agents that are highly effective against serious bacterial infections. METHODS: In our previous study, a series of α-helical AMPs were screened using a novel multiple-descriptor strategy. The current research suggested that S24 exhibited strong antimicrobial activity against major pathogenic bacteria, and displayed minimal haemolysis, good serum stability and maintained salt resistance. RESULTS: We found that S24 exerted an antimicrobial effect by destroying outer membrane permeability and producing a strong binding effect on bacterial genomic DNA that inhibits genomic DNA migration. Furthermore, S24 exerted a strong ability to promote healing in wound infected by P. aeruginosa, A. baumannii and mixed strains in a mouse model. CONCLUSIONS: Overall, S24 showed good stability under physiological conditions and excellent antimicrobial activity, suggesting it may be a potential candidate for the development of serious bacterial infection treatment.
Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Infección de Heridas , Acinetobacter baumannii/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Animales , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Ratones , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/microbiología , Antibacterianos/farmacología , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Modelos Animales de Enfermedad , Permeabilidad de la Membrana Celular/efectos de los fármacos , Humanos , ADN Bacteriano/genéticaRESUMEN
Wound infections are often polymicrobial in nature, biofilm associated and therefore tolerant to antibiotic therapy, and associated with delayed healing. Escherichia coli and Staphylococcus aureus are among the most frequently cultured pathogens from wound infections. However, little is known about the frequency or consequence of E. coli and S. aureus polymicrobial interactions during wound infections. Here we show that E. coli kills Staphylococci, including S. aureus, both in vitro and in a mouse excisional wound model via the genotoxin, colibactin. Colibactin biosynthesis is encoded by the pks locus, which we identified in nearly 30% of human E. coli wound infection isolates. While it is not clear how colibactin is released from E. coli or how it penetrates target cells, we found that the colibactin intermediate N-myristoyl-D-Asn (NMDA) disrupts the S. aureus membrane. We also show that the BarA-UvrY two component system (TCS) senses the environment created during E. coli and S. aureus mixed species interaction, leading to upregulation of pks island genes. Further, we show that BarA-UvrY acts via the carbon storage global regulatory (Csr) system to control pks expression. Together, our data demonstrate the role of colibactin in interspecies competition and show that it is regulated by BarA-UvrY TCS during interspecies competition.
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Infecciones por Escherichia coli , Proteínas de Escherichia coli , Proteínas de la Membrana , Fosfotransferasas , Policétidos , Staphylococcus aureus , Factores de Transcripción , Animales , Antibacterianos/metabolismo , Carbono/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Proteínas de Escherichia coli/metabolismo , Humanos , Proteínas de la Membrana/metabolismo , Ratones , Mutágenos/metabolismo , N-Metilaspartato/metabolismo , Péptidos , Fosfotransferasas/genética , Policétidos/metabolismo , Staphylococcus/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Factores de Transcripción/metabolismo , Infección de Heridas/microbiologíaRESUMEN
BACKGROUND: Bullet-related bacterial wound infection can be caused by high-velocity bullets and shrapnel injuries. In Ethiopia, significant injuries were reported that may cause severe wound infections, persistent systemic infections and may lead to amputation and mortality. The magnitude, antimicrobial susceptibility profiles, and factors associated with bacterial wound infections among patients with bullet-related injuries are not yet studied particularly at health facilities in Bahir Dar, Northwest Ethiopia. Therefore, this study was aimed to determine the prevalence, bacterial profiles, antimicrobial susceptibility profiles, and factors associated with bacterial infections among patients with bullet-related injuries at referral health facilities in Bahir Dar, Northwest Ethiopia. METHODS: A Hospital-based cross-sectional study was conducted among patients with bullet-related injuries at three referral health facilities in Bahir Dar from May 25 to July 27, 2022. A total of 384 patients with bullet-related injuries were included in the study. Sociodemographic and clinical data were collected using a structured questionnaire. Wound swabs were collected aseptically and cultured on Blood and MacConkey agar following bacteriological standards. Biochemical tests were performed to differentiate bacteria for positive cultivation and antimicrobial susceptibility profiles of the isolates were done on Muller Hinton agar using the Kirby-Bauer disk diffusion technique according to the 2021 Clinical Laboratory Standard Institute (CLSI) guideline. The data were entered using Epi-Info version 7.3 and analyzed using SPSS version 25. Descriptive data were presented using frequency, percentages, figures, and charts. Logistic regression was carried out to identify factors associated with bacterial wound infections. P-value < 0.05 was considered statistically significant. RESULTS: The prevalence of bullet-related bacterial wound infection among three referral hospitals in Bahir Dar city was 54.7%. The most commonly isolated Gram-negative organism was Klebsiella spps 49 (23.3%) while among Gram-positive organism, Staphylococcus aureus 58 (27.6%) and coagulase-negative staphylococci (CONS) 18 (8.6%). Contamination, hospitalization and smoking habit were significantly associated with the presence of bullet-related bacterial wound infections. Over 97% multidrug resistant (MDR) bacterial isolates were identified and of theses, E. coli, Proteus species, Citrobactor, and Staphylococcus aureus were highly drug resistant. CONCLUSION: Increased prevalence of bullet-related bacterial wound infection was noticed in this study. S. aureus followed by Klebsiella species were most commonly isolated bacteria. High frequency of resistance to Ampicillin, Oxacillin, Cefepime, Ceftriaxone, Ceftazidime, Vancomycin, and Norfloxacin was observed. Therefore, proper handling of bullet injuries, prompt investigation of bacterial infections, monitoring of drug sensitivity patterns and antibiotic usage are critical.
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Antibacterianos , Pruebas de Sensibilidad Microbiana , Infección de Heridas , Humanos , Etiopía/epidemiología , Masculino , Estudios Transversales , Adulto , Femenino , Prevalencia , Infección de Heridas/microbiología , Infección de Heridas/epidemiología , Antibacterianos/farmacología , Adulto Joven , Heridas por Arma de Fuego/epidemiología , Heridas por Arma de Fuego/microbiología , Infecciones Bacterianas/epidemiología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/tratamiento farmacológico , Persona de Mediana Edad , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/clasificación , Servicio de Urgencia en Hospital/estadística & datos numéricos , AdolescenteRESUMEN
Addressing the complex challenge of healing of bacterially infected wounds, this study explores the potential of lipid nanomaterials, particularly advanced ultradeformable particles (UDPs), to actively influence the wound microenvironment. The research introduces a novel therapeutic approach utilizing silver sulfadiazine (SSD) coupled with vitamin E (VE) delivered through UDPs (ethosomes/transferosomes/transethosomes). Comparative physicochemical characterization of these nanosized drug carriers reveals the superior stability of transethosomes, boasting a zeta potential of -36.5 mV. This method demonstrates reduced side effects compared to conventional therapies, with almost 90% SSD and 72% VE release achieved in wound pH in a sustained manner. Cytotoxicity assessment shows 60% cell viability even at the highest concentration (175 µg/mL), while hemolysis test demonstrates RBC lysis below 5% at a concentration of 250 µg/mL. Vitamin E-SSD-loaded transethosomes (VSTEs) significantly enhance cellular migration and proliferation, achieving 95% closure within 24 h, underscoring their promising efficacy. The synergistic method effectively reduces bacterial burden, evidenced by an 80% reduction in Escherichia coli and Staphylococcus aureus within the wound microenvironment. This approach offers a promising strategy to address complications associated with skin injuries.
Asunto(s)
Portadores de Fármacos , Escherichia coli , Staphylococcus aureus , Vitamina E , Vitamina E/química , Portadores de Fármacos/química , Humanos , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Sulfadiazina de Plata/farmacología , Sulfadiazina de Plata/química , Sulfadiazina de Plata/uso terapéutico , Sulfadiazina de Plata/administración & dosificación , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Animales , Sistemas de Liberación de Medicamentos , Supervivencia Celular/efectos de los fármacosRESUMEN
The present study evaluates the in-vitro antibiofilm activity against the biofilm formed by Staphylococcus aureus, and the wound-healing efficacy of two different types of rhamnolipids produced by Pseudomonas aeruginosa strain JS29 in S.aureus infected wounds. The biosurfactant production was carried out in a mineral salt medium supplemented with 2 % Glucose and 2 % Glycerol individually and thus were designated as RL-Glu and RL-Gly respectively. 0.5 mg/ml of RL-Glu and RL-Gly demonstrated 90 % growth inhibition of S. aureus while exhibiting bactericidal activity at 4 mg/ml of RL-Glu and 1 mg/ml of RL-Gly. Both types of rhamnolipid cause changes in membrane permeability leading to pathogens' non-viability. 90 % inhibition of biofilm formation by S. aureus was observed at 2 mg/ml of RL-Glu and 0.5 mg/ml of RL-Gly, while 0.5 mg/ml of both rhamnolipid disrupted 90 % of the preformed biofilm. 0.5 mg/ml of RL-Glu and RL-Gly decreases the production of exopolysaccharides and also causes structural alteration. 0.5 mg/ml of RL-Glu and RL-Gly were found to exhibit effective wound healing efficacy in S. aureus infected wounds within 7 days of treatment. Histopathological studies of wound sites revealed efficient wound management by both the rhamnolipid. LCMS and GCMS characterization of the biosurfactant revealed that JS29 produces different rhamnolipid congeners when grown on different carbon sources, thereby influencing the antimicrobial, antibiofilm, and wound healing efficacy of rhamnolipid.
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Antibacterianos , Biopelículas , Glucolípidos , Pseudomonas aeruginosa , Staphylococcus aureus , Tensoactivos , Cicatrización de Heridas , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Glucolípidos/farmacología , Staphylococcus aureus/efectos de los fármacos , Tensoactivos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Antibacterianos/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Animales , Pruebas de Sensibilidad Microbiana , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Viabilidad Microbiana/efectos de los fármacos , RatonesRESUMEN
Aim -To isolate bacteriophages targeting extended-spectrum beta-lactamase-producing K. pneumoniae and evaluate their effectiveness across diverse models, incorporating innovative alternatives in animal testing. METHODS AND RESULTS: vB_kpnS-Kpn15 was isolated from sewage sample from Thane district. It produced a clear plaques on K. pneumoniae ATCC 700603. It has a flexible, non-contractile long tail and an icosahedral head and the Siphoviridae family of viruses in the order Caudovirales matched all of its structural criteria. Sequencing of vB_kpnS-Kpn15 revealed a 48,404 bp genome. The vB_KpnS-Kpn15 genome was found to contain 50 hypothetical proteins, of which 16 were found to possess different functions. The vB_KpnS-Kpn15 was also found to possess enzymes for its DNA synthesis. It was found to be lytic for the planktonic cells of K. pneumoniae and bactericidal for up to 48 h and potentially affected established K. pneumoniae biofilms. It demonstrated a broad host range and caused lytic zones on about 46 % of K. pneumoniae multi-drug resistant strains. In an in vitro wound and burn infection model, phage vB_kpnS-Kpn15 in combination with other phages resulted in successful cell proliferation and wound healing. Based on vB_kpnS-Kpn15's lytic properties, it can be incorporated in a bacteriophage cocktail to combat ESBL strains. CONCLUSIONS: The phages isolated during this research are better candidates for phage therapy, and therefore provide new and exciting options for the successful control of antibiotic-resistant bacterial infections in the future. The utilization of animal alternative models in this study elucidates cellular proliferation and migration, underscoring its significance in screening novel drugs with potential applications in the treatment of wound and burn infections. SIGNIFICANCE AND IMPACT OF THE RESEARCH: The findings of this research have implications for the creation of innovative, promising strategies to treat ESBL K. pneumoniae infections.
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Bacteriófagos , Biopelículas , Modelos Animales de Enfermedad , Genoma Viral , Especificidad del Huésped , Infecciones por Klebsiella , Klebsiella pneumoniae , Terapia de Fagos , Aguas del Alcantarillado , beta-Lactamasas , Klebsiella pneumoniae/virología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Animales , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/terapia , Bacteriófagos/genética , Bacteriófagos/aislamiento & purificación , Bacteriófagos/fisiología , Biopelículas/crecimiento & desarrollo , Aguas del Alcantarillado/microbiología , Aguas del Alcantarillado/virología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Humanos , Ratones , Infección de Heridas/microbiología , Infección de Heridas/terapia , Caudovirales/genética , Caudovirales/aislamiento & purificación , Siphoviridae/genética , Siphoviridae/aislamiento & purificación , Siphoviridae/fisiología , Pruebas de Sensibilidad MicrobianaRESUMEN
The growing threat of antimicrobial resistance has made the quest for antibiotic alternatives or synergists one of the most pressing priorities of the 21st century. The emergence of multidrug-resistance in most of the common wound pathogens has amplified the risk of antibiotic-resistant wound infections. Bacteriophages, with their self-replicating ability and targeted specificity, can act as suitable antibiotic alternatives. Nevertheless, targeted delivery of phages to infection sites remains a crucial issue, specifically in the case of topical infections. Hence, different phage delivery systems have been studied in recent years. However, there have been no recent reviews of phage delivery systems focusing exclusively on phage application on wounds. This review provides a compendium of all the major delivery systems that have been used to deliver phages to wound infection sites. Special focus has also been awarded to phage-embedded hydrogels with a discussion on the different aspects to be considered during their preparation.
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Bacteriófagos , Terapia de Fagos , Infección de Heridas , Bacteriófagos/fisiología , Humanos , Infección de Heridas/terapia , Infección de Heridas/microbiología , Terapia de Fagos/métodos , Hidrogeles , Antibacterianos/uso terapéutico , AnimalesRESUMEN
The management of diabetic ulcers poses a significant challenge worldwide, and persistent hyperglycemia makes patients susceptible to bacterial infections. Unfortunately, the overuse of antibiotics may lead to drug resistance and prolonged infections, contributing to chronic inflammation and hindering the healing process. To address these issues, a photothermal therapy technique was incorporated in the preparation of wound dressings. This innovative solution involved the formulation of a self-healing and injectable hydrogel matrix based on the Schiff base structure formed between the oxidized Bletilla striata polysaccharide (BSP) and hydroxypropyltrimethylammonium chloride chitosan. Furthermore, the introduction of CuO nanoparticles encapsulated in polydopamine imparted excellent photothermal properties to the hydrogel, which promoted the release of berberine (BER) loaded on the nanoparticles and boosted the antibacterial performance. In addition to providing a reliable physical protection to the wound, the developed hydrogel, which integrated the herbal components of BSP and BER, effectively accelerated wound closure via microenvironment regulation, including alleviated inflammatory reaction, stimulated re-epithelialization, and reduced oxidative stress based on the promising results from cell and animal experiments. These impressive outcomes highlighted their clinical potential in safeguarding the wound against bacterial intrusion and managing diabetic ulcers.
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Quitosano , Hidrogeles , Polisacáridos , Cicatrización de Heridas , Quitosano/química , Quitosano/análogos & derivados , Quitosano/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Polisacáridos/química , Polisacáridos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Terapia Fototérmica/métodos , Ratones , Humanos , Berberina/farmacología , Berberina/química , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Cobre/química , Cobre/farmacología , Masculino , Polímeros/química , Polímeros/farmacología , Indoles/química , Indoles/farmacología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Nanopartículas/química , Staphylococcus aureus/efectos de los fármacos , Nanopartículas del Metal/químicaRESUMEN
Reactive oxygen species (ROS) have emerged as a promising treatment option for antibacterial and biofilm eradication. However, their therapeutic efficacy is significantly hampered by the unique microenvironments of diabetic wounds. In this study, we designed and synthesized porphyrin-based Fe covalent organic frameworks (Fe-COF) through a Schiff base condensation reaction. Subsequently, Fe-COF were encapsulated with hyaluronic acid (HA) through electrostatic adsorption, resulting in a novel formulation named HA-Fe-COF for diabetic wound healing. HA-Fe-COF were engineered to respond to hyaluronidase in the infected wound, leading to the controlled release of Fe-COF. Those released Fe-COF served a dual role as photosensitizers, generating singlet oxygen and localized heating when exposed to dual light sources. Additionally, they acted as peroxidase-like nanozymes, facilitating the production of ROS through enzymatic reactions. This innovative approach enabled a synergistic therapeutic effect combining photodynamic, photothermal, and chemodynamic modalities. Furthermore, the sustained release of HA from HA-Fe-COF promoted angiogenesis, collagen deposition, and re-epithelialization during the diabetic wound healing process. This "all-in-one" strategy offers a novel approach for the development of antimicrobial and biofilm eradication strategies that minimize damage to healthy tissues in vivo.
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Ácido Hialurónico , Estructuras Metalorgánicas , Porfirinas , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Porfirinas/química , Porfirinas/farmacología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/administración & dosificación , Fármacos Fotosensibilizantes/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Piel/efectos de los fármacos , Humanos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología , Hierro/química , Fotoquimioterapia/métodos , HialuronoglucosaminidasaRESUMEN
The aim of this study was to compare outcomes of moderate and severe foot infections in people with and without diabetes mellitus (DM). We retrospectively evaluated 382 patients (77% with DM and 23% non-DM). We collected demographic data, co-morbidities and one-year outcomes including healing, surgical interventions, number of surgeries, length of stay, re-infection and re-hospitalisation. DM patients required more surgeries (2.3 ± 2.2 vs. 1.7 ± 1.3, p = 0.01), but did not have a longer hospital length of stay during the index hospitalisation (DM 10.9 days ±9.2 vs. non-DM = 8.8 days ±5.8, p = 0.43). After the index hospitalisation, DM patients had increased rates of re-hospitalisation for any reason (63.3% vs. 35.2%, CI 1.9-5.2, OR 3.2, p < 0.01), re-infection at the index wound infection site (48% vs. 30.7%, CI 1.3-3.5, OR 2.1, p < 0.01), re-hospitalisation for a foot pathology (47.3% vs. 29.5%, CI 1.3-3.6, OR 2.1, p < 0.01), and longer times to ulcer healing (151.8 days ±108.8 vs. 108.8 ± 90.6 days, p = 0.04). Patients with DM admitted to hospital with foot infections have worse clinical outcomes during the index hospitalisation and are more likely to have re-infection and re-admission to hospital in the next year.
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Pie Diabético , Tiempo de Internación , Cicatrización de Heridas , Humanos , Pie Diabético/microbiología , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Tiempo de Internación/estadística & datos numéricos , Infección de Heridas/epidemiología , Infección de Heridas/microbiología , Readmisión del Paciente/estadística & datos numéricos , Amputación Quirúrgica/estadística & datos numéricosRESUMEN
An argon-based low-temperature plasma jet (LTPJ) was used to treat chronically infected wounds in Staphylococcus aureus-laden mice. Based on physicochemical property analysis and in vitro antibacterial experiments, the effects of plasma parameters on the reactive nitrogen and oxygen species (RNOS) content and antibacterial capacity were determined, and the optimal treatment parameters were determined to be 4 standard litre per minute and 35 W. Additionally, the plasma-treated activation solution had a bactericidal effect. Although RNOS are related to the antimicrobial effect of plasma, excess RNOS may be detrimental to wound remodelling. In vivo studies demonstrated that medium-dose LTPJ promoted MMP-9 expression and inhibited bacterial growth during the early stages of healing. Moreover, LTPJ increased collagen deposition, reduced inflammation, and restored blood vessel density and TGF-ß levels to normal in the later stages of wound healing. Therefore, when treating chronically infected wounds with LTPJ, selecting the medium dose of plasma is more advantageous for wound recovery. Overall, our study demonstrated that low-temperature plasma jets may be a potential tool for the treatment of chronically infected wounds.
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Gases em Plasma , Staphylococcus aureus , Cicatrización de Heridas , Infección de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratones , Gases em Plasma/farmacología , Infección de Heridas/microbiología , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Infecciones Estafilocócicas , Masculino , Especies de Nitrógeno Reactivo/metabolismoRESUMEN
Bacterial wound infection has emerged as a pivotal threat to human health worldwide, and the situation has worsened owing to the gradual increase in antibiotic-resistant bacteria caused by the improper use of antibiotics. To reduce the use of antibiotics and avoid the increase in antibiotic-resistant bacteria, researchers are increasingly paying attention to photodynamic therapy, which uses light to produce reactive oxygen species to kill bacteria. Treating bacteria-infected wounds by photodynamic therapy requires fixing the photosensitizer (PS) at the wound site and maintaining a certain level of wound humidity. Hydrogels are materials with a high water content and are well suited for fixing PSs at wound sites for antibacterial photodynamic therapy. Therefore, hydrogels are often loaded with PSs for treating bacteria-infected wounds via antibacterial photodynamic therapy. In this review, we systematically summarised the antibacterial mechanisms and applications of PS-loaded hydrogels for treating bacteria-infected wounds via photodynamic therapy. In addition, the recent studies and the research status progresses of novel antibacterial hydrogels are discussed. Finally, the challenges and future prospects of PS-loaded hydrogels are reviewed.