RESUMEN
Prophages are prevalent among bacterial species, including strains carrying antibiotic resistance genes (ARGs). Prophage induction can be triggered by the SOS response to stressors, leading to cell lysis. In environments polluted by chemical stressors, ARGs and prophage co-harboring strains might pose an unknown risk of spreading ARGs through chemical pollutant-mediated prophage induction and subsequent cell lysis. In this study, we investigated the effects of common non-antibiotic water pollutants, triclosan and silver nanoparticles, on triggering prophage induction in clinical isolates carrying ARGs and the subsequent uptake of released ARGs by the naturally competent bacterium Acinetobacter baylyi. Our results demonstrate that both triclosan and silver nanoparticles, at environmentally relevant concentrations and those found in commercial products, significantly enhance prophage induction among various clinical isolates. Transmission electron microscopy imaging and plaque assays confirmed the production of infectious phage particles under non-antibiotic pollutants-mediated prophage induction. In addition, the rate of ARG transformation to A. baylyi significantly increased after the release of extracellular ARGs from prophage induction-mediated cell lysis. The mechanism of non-antibiotic pollutants-mediated prophage induction is primarily associated with excessive oxidative stress, which provokes the SOS response. Our findings offer insights into the role of non-antibiotic pollutants in promoting the dissemination of ARGs by triggering prophage induction.
Asunto(s)
Profagos , Profagos/genética , Acinetobacter/efectos de los fármacos , Acinetobacter/genética , Farmacorresistencia Microbiana/genética , Triclosán/farmacología , Farmacorresistencia Bacteriana/genética , Antibacterianos/farmacología , Nanopartículas del Metal , Plata/farmacologíaRESUMEN
Triclosan (TCS) is a widely used antimicrobial, antifungal, and antiviral agent. To date, it has been reported that TCS can enter the human body and disrupt hormonal homeostasis. Therefore, the aim of our paper was to evaluate the impact of TCS on astrocytes, i.e. a crucial population of cells responsible for steroid hormone production. Our data showed that, in mouse primary astrocyte cultures, TCS can act as an endocrine disrupting chemical through destabilization of the production or secretion of progesterone (P4), testosterone (T), and estradiol (E2). TCS affects the mRNA expression of enzymes involved in neurosteroidogenesis, such as Cyp17a1, 17ß-Hsd, and Cyp19a1. Our data showed that a partial PPARγ agonist (honokiol) prevented changes in Cyp17a1 mRNA expression caused by TCS. Similarly, honokiol inhibited TCS-stimulated P4 release. However, rosiglitazone (classic PPARγ agonist) or GW9662 (PPARγ antagonist) had a much stronger effect. Therefore, we believe that the changes observed in the P4, T, and E2 levels are a result of dysregulation of the activity of the aforementioned enzymes, whose expression can be affected by TCS through a Pparγ-dependent pathway. TCS was found to decrease the aryl hydrocarbon receptor (AhR) and Sirtuin 3 protein levels, which may be the result of the activation of the these proteins. Since our study showed dysregulation of the production or secretion of neurosteroids in astrocytes, it can be concluded that TCS reaching the brain may contribute to the development of neurodegenerative diseases in which an abnormal amount of neurosteroids is observed.
Asunto(s)
Astrocitos , Progesterona , Sirtuina 1 , Sirtuina 3 , Triclosán , Animales , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Triclosán/farmacología , Ratones , Células Cultivadas , Progesterona/metabolismo , Sirtuina 1/metabolismo , Sirtuina 1/genética , Sirtuina 3/metabolismo , Sirtuina 3/genética , PPAR gamma/metabolismo , PPAR gamma/genética , Estradiol/farmacología , Estradiol/metabolismo , Testosterona/metabolismo , Esteroide 17-alfa-Hidroxilasa/metabolismo , Esteroide 17-alfa-Hidroxilasa/genética , Disruptores Endocrinos/farmacología , Compuestos de Bifenilo/farmacología , Rosiglitazona/farmacologíaRESUMEN
Triclosan (TCS), a hydrophobic antibacterial agent, is extensive application in daily life. Despite a low biodegradability rate, its hydrophobicity results in its accumulation in waste-activated sludge (WAS) during domestic and industrial wastewater treatment. While anaerobic digestion is the foremost strategy for WAS treatment, limited research has explored the interphase migration behavior and impacts of TCS on WAS degradation during anaerobic digestion. This study revealed TCS migration between solid- and liquid-phase in WAS digestion. The solid-liquid distribution coefficients of TCS were negative for proteins and polysaccharides and positive for ammonium. High TCS levels promoted volatile-fatty-acid accumulation and reduced methane production. Enzyme activity tests and functional prediction indicated that TCS increased enzyme activity associated with acid production, in contrast to the inhibition of key methanogenic enzymes. The findings of the TCS migration behavior and its impacts on WAS anaerobic digestion provide an in-depth understanding of the evolution of enhanced TCS-removing technology.
Asunto(s)
Metano , Aguas del Alcantarillado , Triclosán , Triclosán/farmacología , Triclosán/metabolismo , Anaerobiosis , Metano/metabolismo , Biodegradación Ambiental , Ácidos Grasos Volátiles/metabolismo , Reactores Biológicos , Contaminantes Químicos del Agua/metabolismo , Eliminación de Residuos Líquidos/métodosRESUMEN
Aim: The WHO, Global tuberculosis report 2022 estimated number of tuberculosis (TB) cases reached 10.6 million in 2021, reflecting a 4.5% increase compared with the 10.1 million reported in 2020. The incidence rate of TB showed 3.6% rise from 2020 to 2021. Results/methodology: This manuscript discloses Cu-promoted single pot A3-coupling between triclosan (TCS)-based alkyne, formaldehyde and secondary amines to yield TCS-based Mannich adducts. Additionally, the coupling of TCS-alkynes in the presence of Cu(OAc)2 afforded the corresponding homodimers. Among tested compounds, the most potent one in the series 11 exhibited fourfold higher potency than rifabutin against drug-resistant Mycobacterium abscessus. The selectivity index was also substantially improved, being 26 (day 1) and 15 (day 3), which is four-times better than TCS.
[Box: see text].
Asunto(s)
Cobre , Pruebas de Sensibilidad Microbiana , Triclosán , Triclosán/farmacología , Triclosán/química , Triclosán/síntesis química , Cobre/química , Cobre/farmacología , Estructura Molecular , Antituberculosos/farmacología , Antituberculosos/química , Antituberculosos/síntesis química , Mycobacterium abscessus/efectos de los fármacos , Simulación por Computador , Relación Estructura-Actividad , Humanos , Bases de Mannich/química , Bases de Mannich/farmacología , Bases de Mannich/síntesis químicaRESUMEN
Among the ESKAPE pathogens, Pseudomonas aeruginosa is an extensively notorious superbug that causes difficult-to-treat infections. Since quorum sensing (QS) directly promotes pseudomonal virulence, targeting QS circuits is a promising approach for disarming phenotypic virulence. Hence, this study scrutinizes the anti-QS, antivirulence, and anti-biofilm potential of citral (CiT; phytochemical) and triclosan (TcN; disinfectant), alone and in combination, against P. aeruginosa PAO1/PA14. The findings confirmed synergism between CiT and TcN and revealed their quorum quenching (QQ) potential. At sub-inhibitory levels, CiT-TcN combination significantly impeded pyocyanin, total bacterial protease, hemolysin, and pyochelin production alongside inhibiting biofilm formation in P. aeruginosa. Moreover, the QQ and antivirulence potential of CiT and TcN was positively correlated by molecular docking studies that predicted strong associations of the drugs with QS receptors of P. aeruginosa. Collectively, the study identifies CiT-TcN as an effective drug combination that harbors QQ, antivirulence, and anti-biofilm prospects against P. aeruginosa.
Asunto(s)
Monoterpenos Acíclicos , Antibacterianos , Biopelículas , Sinergismo Farmacológico , Simulación del Acoplamiento Molecular , Pseudomonas aeruginosa , Percepción de Quorum , Triclosán , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/fisiología , Percepción de Quorum/efectos de los fármacos , Triclosán/farmacología , Biopelículas/efectos de los fármacos , Monoterpenos Acíclicos/farmacología , Antibacterianos/farmacología , Virulencia/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Piocianina/metabolismoRESUMEN
Triclosan is a potent antibacterial compound widely used in everyday products. Whether triclosan affects Leydig cell function in adult male rats remains unknown. In this study, 0, 50, 100, or 200 mg/kg/day triclosan was gavaged to Sprague-Dawley male rats from 56 to 63 days postpartum. Triclosan significantly reduced serum testosterone levels at ≥ 50 mg/kg/day via downregulating the expression of Leydig cell gene Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd17b3 and regulatory transcription factor Nr3c2 at 100-200 mg/kg. Further analysis showed that triclosan markedly increased autophagy as shown by increasing LC3II and BECN1 and decreasing SQSTM1. The mRNA m6A modification analysis revealed that triclosan significantly downregulated Fto expression at 200 mg/kg while upregulating Ythdf1 expression at 100 and 200 mg/kg, leading to methylation of Becn1 mRNA as shown by MeRIP assay. Triclosan significantly inhibited testosterone output in rat R2C Leydig cells at ≥ 5 µM via downregulating Fto and upregulating Ythdf1. SiRNA Ythdf1 knockdown can reverse triclosan-mediated mitophagy in R2C cells, thereby reversing the reduction of testosterone output. In summary, triclosan caused Becn1 m6A methylation by downregulating Fto and upregulating Ythdf1, which accelerated Becn1 translation, thus leading to the occurrence of autophagy and the decrease of testosterone biosynthesis.
Asunto(s)
Autofagia , Células Intersticiales del Testículo , Ratas Sprague-Dawley , Testosterona , Triclosán , Animales , Masculino , Autofagia/efectos de los fármacos , Testosterona/sangre , Testosterona/biosíntesis , Ratas , Triclosán/toxicidad , Triclosán/farmacología , Células Intersticiales del Testículo/efectos de los fármacos , Células Intersticiales del Testículo/metabolismo , MetilaciónRESUMEN
Bioabsorbable sutures can improve the medical functions of existing non-absorbable sutures, and may produce new medical effects, and are expected to become a new generation of medical degradable materials. In this study, the cytocompatibility of triclosan coated polyglactin910 sutures (CTS-PLGA910) was analyzed and different concentrations of sutures were prepared. The effects of sutures on the cytotoxicity and cell proliferation of HUVEC were studied by CCK-8 assay. The hemolysis, total antioxidant capacity (T-AOC) activity and nitric oxide (NO) content were investigated to improve the blood compatibility of sutures. The results showed that the hemolysis rate of CTS-PLGA910 was less than 5%. After treatment on HUVEC cells for 48 and 72 h, there was no significant change in NO content in CTS-PLGA910 groups compared with the control group, while T-AOC activity and antioxidant capacity were significantly increased in medium and high dose groups. In summary, the blood compatibility and cell compatibility were significantly improved, which provided a basis for the clinical application of sutures in the future.
Asunto(s)
Proliferación Celular , Materiales Biocompatibles Revestidos , Células Endoteliales de la Vena Umbilical Humana , Ensayo de Materiales , Poliglactina 910 , Suturas , Triclosán , Humanos , Triclosán/farmacología , Triclosán/química , Poliglactina 910/química , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Proliferación Celular/efectos de los fármacos , Hemólisis/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/química , Materiales Biocompatibles/química , Óxido Nítrico/metabolismo , Supervivencia Celular/efectos de los fármacosRESUMEN
Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor alpha (PPARα), and stress sensor, activating transcription factor 4 (ATF4). When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep) and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.
Asunto(s)
Factor de Transcripción Activador 4 , Animales Recién Nacidos , Bilirrubina , Glucuronosiltransferasa , Hígado , PPAR alfa , Triclosán , Animales , Glucuronosiltransferasa/metabolismo , Glucuronosiltransferasa/genética , PPAR alfa/metabolismo , PPAR alfa/genética , Ratones , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/genética , Triclosán/farmacología , Humanos , Bilirrubina/farmacología , Bilirrubina/metabolismo , Hígado/metabolismo , Hígado/efectos de los fármacos , Ratones Noqueados , Femenino , Receptor de Androstano Constitutivo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/genéticaRESUMEN
Triclosan (TCS) and tetracycline (TC) are commonly detected antibacterial agents in sewage and environment matrices. Nonetheless, the impact of sequential exposure to TCS and TC on the methanogenic digestion microbiome remains unknown. In this study, TCS was shown to reduce COD removal efficiency to 69.8%, but alleviated the inhibitive effect of consequent TC-amendment on the digestion microbiome. Interestingly, TCS pre-exposure resulted in abundance increase of acetotrophic Methanosaeta to 2.68%, being 2.91 folds higher than that without TCS amendment. Microbial network analyses showed that TCS pre-exposure caused microorganisms to establish a co-ecological relationship against TC disturbance. Further analyses of total antibiotic resistance genes (ARGs) showed the TCS-derived compromise of TC-induced ARGs enrichment in digestion microbiomes, e.g., 238.2% and 152.1% ARGs increase upon TC addition in digestion microbiomes without and with TCS pre-exposure, respectively. This study provides new insights into the impact of antibacterial agents on the methanogenic digestion microbiome.
Asunto(s)
Metano , Microbiota , Tetraciclina , Triclosán , Triclosán/farmacología , Microbiota/efectos de los fármacos , Tetraciclina/farmacología , Metano/metabolismo , Farmacorresistencia Microbiana/genética , Aguas del Alcantarillado/microbiología , Antibacterianos/farmacologíaRESUMEN
Skin injuries infected by bacteria can cause life-threatening human diseases if not treated properly. In this work, we developed a light-degradable nanocomposite hydrogel to achieve both controlled antibiotic delivery and hydrogel degradation using light as the sole stimulus. Specifically, we incorporated triclosan-loaded, poly(N-isopropylacrylamide)-based nanogels (TCS-NGs) that exhibited potent antibacterial efficacy, into a light-degradable poly (ethylene glycol) (PEG)-based hydrogel matrix via simple physical entrapment method. Upon exposure to 365 nm light, the hydrogel matrix could rapidly degrade, which subsequently released the entrapped TCS-NGs into the surrounding environment. Our results demonstrated that TCS-NGs released from light-degradable nanocomposite hydrogels still possessed remarkable antibacterial efficacy by inhibiting the growth of Staphylococcus aureus both in solution (a fivefold reduction in optical density compared to the blank control) and on bacteria-infected porcine skins (a fivefold reduction in colony-forming units compared to the blank control). Finally, using an alamarBlue assay on human dermal fibroblasts, we determined that each component of the nanocomposite hydrogel exhibited excellent biocompatibility (>90% cell viability) and would not cause significant cytotoxicity. Overall, the fabricated light-degradable nanocomposite hydrogels could serve as novel material for antibacterial wound dressing applications.
Asunto(s)
Antibacterianos , Vendajes , Hidrogeles , Luz , Nanocompuestos , Staphylococcus aureus , Antibacterianos/química , Antibacterianos/farmacología , Staphylococcus aureus/efectos de los fármacos , Nanocompuestos/química , Hidrogeles/química , Hidrogeles/farmacología , Hidrogeles/síntesis química , Animales , Humanos , Porcinos , Pruebas de Sensibilidad Microbiana , Nanogeles/química , Cicatrización de Heridas/efectos de los fármacos , Polietilenglicoles/química , Supervivencia Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Triclosán/química , Triclosán/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacologíaRESUMEN
The horizontal transfer of plasmids has been recognized as one of the key drivers for the worldwide spread of antimicrobial resistance (AMR) across bacterial pathogens. However, knowledge remain limited about the contribution made by environmental stress on the evolution of bacterial AMR by modulating horizontal acquisition of AMR plasmids and other mobile genetic elements. Here we combined experimental evolution, whole genome sequencing, reverse genetic engineering, and transcriptomics to examine if the evolution of chromosomal AMR to triclosan (TCS) disinfectant has correlated effects on modulating bacterial pathogen (Klebsiella pneumoniae) permissiveness to AMR plasmids and phage susceptibility. Herein, we show that TCS exposure increases the evolvability of K. pneumoniae to evolve TCS-resistant mutants (TRMs) by acquiring mutations and altered expression of several genes previously associated with TCS and antibiotic resistance. Notably, nsrR deletion increases conjugation permissiveness of K. pneumoniae to four AMR plasmids, and enhances susceptibility to various Klebsiella-specific phages through the downregulation of several bacterial defense systems and changes in membrane potential with altered reactive oxygen species response. Our findings suggest that unrestricted use of TCS disinfectant imposes a dual impact on bacterial antibiotic resistance by augmenting both chromosomally and horizontally acquired AMR mechanisms.
Asunto(s)
Bacteriófagos , Klebsiella pneumoniae , Plásmidos , Triclosán , Triclosán/farmacología , Plásmidos/genética , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/virología , Bacteriófagos/genética , Bacteriófagos/fisiología , Farmacorresistencia Bacteriana Múltiple/genética , Mutación , Transferencia de Gen Horizontal , Secuenciación Completa del Genoma , Evolución Molecular , Antibacterianos/farmacologíaRESUMEN
AIMS: To evaluate the effect of silver nanoparticles alone and in combination with Triclosan, and trans-cinnamaldehyde against Staphylococcus aureus and Escherichia coli biofilms on sutures to improve patients' outcomes. METHODS AND RESULTS: Silver nanoparticles were prepared by chemical method and characterized by UV-visible spectrophotometer and dynamic light scattering. The minimum inhibitory concentration was assessed by the Microdilution assay. The antibiofilm activity was determined using crystal violet assay. A checkerboard assay using the fractional inhibitory concentration index and time-kill curve was used to investigate the synergistic effect of silver nanoparticle combinations. The hemolytic activity was determined using an erythrocyte hemolytic assay. Our results revealed that silver nanoparticles, Triclosan, and trans-cinnamaldehyde (TCA) inhibited S.aureus and E.coli biofilms. Silver nanoparticles with TCA showed a synergistic effect (FICI values 0.35 and 0.45 against S. aureus and E. coli biofilms, respectively), and silver nanoparticles with Triclosan showed complete inhibition of S. aureus biofilm. The hemolytic activity was <2.50% for the combinations.
Asunto(s)
Acroleína/análogos & derivados , Antiinfecciosos , Nanopartículas del Metal , Triclosán , Humanos , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Staphylococcus aureus , Triclosán/farmacología , Escherichia coli , Antibacterianos/farmacología , Antibacterianos/química , Antiinfecciosos/farmacología , Biopelículas , Suturas , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVE: The aim of this scoping review was to explore and synthesise the current evidence on the antimicrobial activity of antibacterial suture materials used in oral surgery. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews. A bibliographic search was carried out in the PubMed and Scopus databases to retrieve all human clinical studies that investigated the antimicrobial efficacy of antibacterial-coated sutures used in oral surgery. Included studies were screened and extracted independently by 2 examiners. Data were tabulated and qualitatively described. RESULTS: The search initially returned 150 articles and resulted in 5 included studies after the duplicates' removal and the full-text screening. Selected studies were published from 2014 to 2019. Three studies (60%) were randomised clinical trials, whilst the remaining studies did not report information on randomisation. The antimicrobial agents for coated sutures included triclosan and chlorhexidine. In almost all the studies, antibacterial-coated sutures exhibited lower bacterial retention compared to those without coating. CONCLUSIONS: Within limitations, the antimicrobial-coated sutures employed in oral surgery exhibited good results in terms of their microbicidal activity when compared with sutures that were not coated. Considering the high variability and confounding factors identified in the included studies, more high-quality research is needed to confirm these results. Antimicrobial-coated sutures could represent a promising and clinically valid strategy to reduce microbial colonisation in oral surgery. The reduced bacterial adherence is likely to improve the clinical success of the surgical procedures. Yet, the cost-benefit ratio of antimicrobial-coated sutures should be assessed in larger clinical trials to confirm their efficacy over conventional noncoated sutures.
Asunto(s)
Antibacterianos , Suturas , Humanos , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Procedimientos Quirúrgicos Orales , Infección de la Herida Quirúrgica/prevención & control , Antiinfecciosos Locales/uso terapéutico , Antiinfecciosos Locales/farmacología , Clorhexidina/uso terapéutico , Clorhexidina/farmacología , Triclosán/farmacología , Triclosán/uso terapéuticoRESUMEN
Several facets of the host response to tuberculosis have been tapped for clinical investigation, especially targeting angiogenesis mediated by VEGF signaling from infected macrophages. Herein, we rationalized combining the antiangiogenic effects of VEGFR-2 blockade with direct antitubercular InhA inhibition in single hybrid dual inhibitors as advantageous alternatives to the multidrug regimens. Inspired by expanded triclosans, the ether ligation of triclosan was replaced by rationalized linkers to assemble the VEGFR-2 inhibitors thematic scaffold. Accordingly, new series of 3-(p-chlorophenyl)-1-phenylpyrazole derivatives tethered to substituted ureas and their isosteres were synthesized, evaluated against Mycobacterium tuberculosis virulent cell line H37Rv, and assessed for their InhA inhibitory activities. The urea derivatives 8d and 8g exhibited the most promising antitubercular activity (MIC = 6.25 µg/mL) surpassing triclosan (MIC = 20 µg/mL) with potential InhA inhibition, thus identified as the study hits. Interestingly, both compounds inhibited VEGFR-2 at nanomolar IC50 (15.27 and 24.12 nM, respectively). Docking and molecular dynamics simulations presumed that 8d and 8g could bind to their molecular targets InhA and VEGFR-2 posing essential stable interactions shared by the reference inhibitors triclosan and sorafenib. Finally, practical LogP, Lipinski's parameters and in silico ADMET calculations highlighted their drug-likeness as novel leads in the arsenal against TB.
Asunto(s)
Mycobacterium tuberculosis , Triclosán , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Relación Estructura-Actividad , Triclosán/farmacología , Antituberculosos/farmacología , Pirazoles/farmacología , Simulación del Acoplamiento Molecular , Proteínas Bacterianas/metabolismoRESUMEN
Considering the differences in pH between bacterial infection microenvironment and normal tissues, a series of pH-responsive drug-release amphiphilic polyurethane copolymers (DPU-g-PEG) have been prepared in this work. Fourier transform infrared (FT-IR) spectroscopy and 1H NMR was selected to detect the structure of the condensed polymers. The DPU-g-PEG amphiphilic copolymers could form stable micelles with a hydrophilic shell of polyethylene glycol (PEG) and a hydrophobic core of polylactic acid (PLA). We loaded a model drug called triclosan onto DPU-g-PEG micelles and studied how pH affects their particle size, Zeta potential, and drug release performance. The results revealed that when exposed to acidic conditions, the surface potential of DPU-g-PEG micelles changed, the micelles' particle size increased, and the drug release performance was significantly enhanced. These results suggested that the micelles prepared in this study can release more antibacterial substances at sites of bacterial infection. Meanwhile, we also investigated the impact of different ratios of soft and hard segments on the properties of micelles, and the results showed that the pH responsiveness of micelles was strongest when the ratio of soft segments (PLLA diol + PEG 2000): 1,6-hexamethylene diisocyanate (HDI): 2,6-Bis-(2-hydroxy-ethyl)-pyrrolo[3,4-f]isoindole-1,3,5,7-tetraone (DMA) = 1: 1.2: 0.2. Furthermore, the results of inhibition zone test, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) all confirmed the antibacterial activity of triclosan-load DPU-g-PEG micelles. In conclusion, the DPU-g-PEG micelles produced in this study have the potential to be used as intelligent drug delivery systems in the biomedical field.
Asunto(s)
Infecciones Bacterianas , Triclosán , Humanos , Micelas , Poliuretanos/química , Portadores de Fármacos/química , Triclosán/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , Polietilenglicoles/química , Polímeros/química , Antibacterianos/farmacología , Concentración de Iones de HidrógenoRESUMEN
Despite advancements in preventive measures and hospital protocols, surgical site infections (SSIs) remain a significant concern following surgeries. Sutures, commonly used for wound closure, can serve as a platform for microbial adherence and contamination, leading to extensive debridement and recurrent antibiotic therapy. The emergence of drug resistance and the formation of biofilms on sutures have further complicated the management of SSIs. Drug-eluting sutures incorporating biocides like triclosan have limitations due to uncontrolled release and associated toxicity. Therefore, there is a need for alternative approaches to impart antimicrobial properties to sutures. In this study, we present a one-step covalent cross-linking method to coat surgical sutures with an antimicrobial small molecule, quaternary benzophenone-based antimicrobial (QSM). Additionally, the sutures are dip-coated with ibuprofen, a nonsteroidal anti-inflammatory drug with analgesic properties. The coated sutures maintained their morphological and tensile properties after in vivo implantation. The antimicrobial coating demonstrated efficacy against a broad-spectrum pathogens, including drug-resistant bacteria and fungi. The optimized formulation retained its biodegradability in vivo. Furthermore, the coated sutures exhibited â¼3 log reduction in methicillin-resistant Staphylococcus aureus (MRSA) burden in a subcutaneous implantation mouse model. Overall, this multifunctional coating provides antimicrobial properties to surgical sutures while preserving their mechanical integrity and biodegradability. These coated sutures have the potential to address the challenge of SSIs and contribute to improved surgical outcomes.
Asunto(s)
Antiinfecciosos , Staphylococcus aureus Resistente a Meticilina , Triclosán , Animales , Ratones , Infección de la Herida Quirúrgica/tratamiento farmacológico , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/microbiología , Suturas/efectos adversos , Triclosán/farmacologíaRESUMEN
Antimicrobial disinfectants have been extensively used to control hospital-acquired infections worldwide. Prolonged exposure to bacteria could promote resistance to antimicrobial disinfectants. This study evaluated the antimicrobial activity of four commonly used disinfectants; triclosan, chlorhexidine digluconate, benzalkonium chloride, and formaldehyde against Acinetobacter baumannii clinical isolates. This study also determined the prevalence and association of efflux pumps encoding genes qacE, qacED1, emrA, and aceI with tolerance to disinfectants. A total of 100 A. baumannii isolates were included in the current study. The antimicrobial disinfectants' minimum inhibitory concentration (MIC) was determined using an agar dilution method. Genes involved in resistance to disinfectants were investigated by PCR method. The benzalkonium chloride MICs ranged between 32 and 128 µg mL-1, chlorhexidine digluconate 8-64 µg mL-1, triclosan 1-32 µg mL-1, and formaldehyde 128 µg mL-1. Overall, the highest MIC90 value was identified for formaldehyde (128 µg mL-1), followed by benzalkonium chloride and chlorhexidine digluconate (64 µg mL-1, each one) and triclosan (4 µg mL-1). In the present study, the qacE, qacED1, emrA, and aceI genes were found in 91%, 55%, 100%, and 88% of isolates, respectively. The qacG gene was not identified in our A. baumannii isolates. The qacED1 gene was associated with higher MICs for all disinfectants tested (P < 0.05), while the qacE and aceI genes were associated with higher MICs for benzalkonium chloride and chlorhexidine. This study indicated that triclosan is the most effective disinfectant against A. baumannii isolates.
Asunto(s)
Acinetobacter baumannii , Desinfectantes , Triclosán , Desinfectantes/farmacología , Triclosán/farmacología , Compuestos de Benzalconio/farmacología , Irán , Formaldehído/farmacología , Mitomicina/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacologíaRESUMEN
OBJECTIVE: The oral cavity is a colossal reservoir for the bacteria. The healing of tissues is compromised after flap surgery, particularly in the presence of sutures, as they can act as repositories for bacteria, ultimately leading to surgical site infections. Hence, antibacterial-coated sutures have been considered as an alternative to reduce the risk of these infections and further improve the wound healing of the tissues after flap surgery. Since minimal information is available on the effect of antibacterial-coated sutures on periodontal tissues, this study aims to clinically and microbiologically assess the antibacterial efficacy of Triclosan (TCS) and Chlorhexidine-coated sutures (CCS) on periodontal tissues compared to non-coated sutures (NCS). PATIENTS AND METHODS: A total of 75 subjects with moderate to severe periodontitis were included in the study and randomly allocated to one of the three groups, (TCS, CCS, and NCS groups) equally. Suture removal was performed on postoperative day 8, and parameters such as wound healing and post-operative pain were evaluated. The retrieved suture samples were subjected to microbiological analysis and the bacteria were identified quantitatively and qualitatively. RESULTS: Intragroup analysis of the wound healing index and post-operative pain for all the groups showed a significant improvement (p<0.01), from day 8 to day 30. Intergroup analysis of the wound healing index revealed significant wound healing (p<0.05) on day 15 and day 30. For post-operative pain, intergroup analyses showed significantly low pain scores (p<0.01) for the TCS group. Microbiologic analysis of aerobic colony counts in both anterior and posterior regions revealed significantly (p<0.01) least colony counts in TCS and highest colony counts in NCS groups, respectively. Although anaerobic colony counts were not statistically significant, relatively fewer colony counts were identified in the TCS group. Whereas, relatively higher anaerobic colony counts were seen in the CCS group in the anterior region and in the NCS group in the posterior region. Qualitative assessment revealed higher amounts of Streptococcus and Staphylococcus species in all the three groups (TCS, CCS, and NCS groups). CONCLUSIONS: Antibacterial-coated sutures, particularly Triclosan-coated sutures, are effective in reducing bacterial accumulation compared to non-coated sutures. Therefore, these sutures can be effectively utilized in periodontal flap surgery.
Asunto(s)
Antiinfecciosos Locales , Triclosán , Humanos , Triclosán/farmacología , Clorhexidina/farmacología , Antiinfecciosos Locales/farmacología , Antibacterianos , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/microbiología , Suturas/microbiología , Bacterias , Dolor PostoperatorioRESUMEN
Surgical sutures designed to prevent infection are critical in addressing antibiotic-resistant pathogens that cause surgical site infections. Instead of antibiotics, alternative materials such as biocides have been assessed for coating commercially used sutures due to emerging antibiotic resistance concerns worldwide. This study has a new approach to the development of fibrous surgical sutures with the ability to deliver localized antibacterial agents. A new manufacturing process based on pressure spinning was used for the first time in the production of fibrous surgical sutures by physically blending antibacterial triclosan (Tri) agent with poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene oxide) (PEO) polymers. Fibrous surgical sutures with virgin PLGA, virgin PEO, different ratios of PLGA-PEO, and different ratios of Tri-loaded PLGA-PEO fibrous sutures were produced to mimic the FDA- and NICE-approved PLGA-based sutures available in the market and compared for their characteristics. They were also tested simultaneously with commercially available sutures to compare their in vitro biodegradation, antibacterial, drug release, and cytotoxicity properties. After in vitro antibacterial testing for 24 h, sutures having 285 ± 12 µg/mg Tri loading were selected as a model for further testing as they exhibited antibacterial activity against all tested bacteria strains. The selected model of antibacterial fibrous sutures exhibited an initial burst of Tri release within 24 h, followed by a sustained release for the remaining time until the sutures completely degraded within 21 days. The cell viability assay showed that these surgical sutures had no cytotoxic effect on mammalian cells.
Asunto(s)
Antibacterianos , Triclosán , Animales , Antibacterianos/farmacología , Suturas , Triclosán/farmacología , Polímeros , MamíferosRESUMEN
The presence of bacterial biofilms has presented a significant challenge to human health. This study presents the development of biofilm microenvironment-responsive polymeric micelles as a novel approach to address the challenges posed by bacterial biofilms. These micelles are composed of two key components: a zwitterionic component, inspired by protein isoelectric points, containing balanced quantities of primary amines and carboxylic groups that undergo a positive charge transformation in acidic microenvironments, and a hydrophobic triclosan conjugate capable of releasing triclosan in the presence of bacterial lipases. Through the synergistic combination of pH-responsiveness and lipase-responsiveness, we have significantly improved drug penetration into biofilms and enhanced its efficacy in killing bacteria. With their remarkable drug-loading capacity and the ability to specifically target and eliminate bacteria within biofilms, these zwitterionic polymeric micelles hold great promise as an effective alternative for treating biofilm-associated infections. Their unique properties enable efficient drug delivery and heightened effectiveness against biofilm-related infections.