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The biofilms formed by bacteria at the wound site can effectively protect the bacteria, which greatly weakens the effect of antibiotics. Herein, a microneedle patch for wound ...treatment is designed, which can effectively penetrate the biofilms in a physical way because of the penetration ability of the microneedles and the motion behavior of the nanomotors, and deliver bacterial quorum sensing inhibitor luteolin (Le) and nanomotors with multiple antibacterial properties within biofilms. Firstly, the nanomotors-loaded microneedle patches are prepared and characterized. The results of in vitro and in vivo experiments show that the microneedle patches have good biosafety and antibacterial properties. Among them, Le can inhibit the growth of biofilms. Further, under near-infrared (NIR) irradiation, the nanomotors loaded with photosensitizer ICG and nitric oxide (NO) donor L-arginine (L-Arg) can move in the biofilms under the double driving effect of photothermal and NO, and can give full play to the multiple anti-biological infection effects of photothermal therapy (PTT), photodynamic therapy (PDT) and NO, and finally realize the effective removal of biofilms and promote wound healing. The intervention of nanomotor technology has brought about a new therapeutic strategy for bacterial biofilm-related infection of wound.
Central-line-associated bloodstream infections are increasingly recognized to be associated with intraluminal microbial biofilms, and effective measures for the prevention and treatment of ...bloodstream infections remain lacking. This report evaluates a new commercially developed antimicrobial catheter lock solution (ACL), containing trimethoprim (5 mg/ml), ethanol (25%), and calcium EDTA (Ca-EDTA) (3%), for activity against bacterial and fungal biofilms, using
and
(rabbit) catheter biofilm models. Biofilms were formed by bacterial (seven different species, including vancomycin-resistant
VRE) or fungal (
) species on catheter materials. Biofilm formation was evaluated by quantitative culture (CFU) and scanning electron microscopy (SEM). Treatment with ACL inhibited the growth of adhesion-phase biofilms
after 60 min (VRE) or 15 min (all others), while mature biofilms were completely inhibited after exposure for 2 or 4 h, compared to control. Similar results were observed for drug-resistant bacteria. Compared to the heparinized saline controls, ACL lock therapy significantly reduced the catheter bacterial (3.49 ± 0.75 versus 0.03 ± 0.06 log CFU/catheter;
= 0.016) and fungal (2.48 ± 1.60 versus 0.55 ± 1.19 log CFU/catheter segment;
= 0.013) burdens in the catheterized rabbit model. SEM also demonstrated eradication of bacterial and fungal biofilms
on catheters exposed to ACL, while vigorous biofilms were observed on untreated control catheters. Our results demonstrated that ACL was efficacious against both adhesion-phase and mature biofilms formed by bacteria and fungi
and
.
Conventional drugs used for antibacterial therapy display several limitations. This is not due to antibiotics being ineffective, but rather due to their low bioavailability, limited penetration to ...sites of infection and the rise of drug-resistant bacteria. Although new delivery systems (e.g., nanoparticles) that are loaded with antibacterial drugs have been designed to overcome these limitations, therapeutic efficacy does not seem to have improved. Against this backdrop, stimuli-responsive antibiotic-loaded nanoparticles and materials with antimicrobial properties (nanoantibiotics) present the ability to enhance therapeutic efficacy, while also reducing drug resistance and side effects. These stimuli can either be exogenous (e.g., light, ultrasound) or endogenous (e.g., pH, variation in redox gradient, enzymes). This promising therapeutic approach relies on advances in materials science and increased knowledge of microorganism growth and biofilm formation. This review provides an overview in the field of antibacterial drug-delivery systems and nanoantibiotics that benefit from a response to specific triggers, and also presents a number of future prospects.
This study was designed to evaluate the
antimicrobial activity of amlodipine against
strains.
The antimicrobial activity of amlodipine was evaluated by the broth microdilution method and its ...interaction with oxacillin was evaluated by checkerboard assay. The possible mechanism of action was evaluated by flow cytometry and molecular docking techniques.
Amlodipine showed activity against
between 64 and 128 μg/ml, in addition to showing synergism in approximately 58% of the strains used. Amlodipine also showed good activity against forming and mature biofilms. The possible mechanism of action may be attributed to its ability to lead to cell death.
Amlodipine has antibacterial activity against
.
Dissolving microneedles (MN) with enhanced physiochemical properties are generating considerable interest as antibacterial delivery devices, which minimize hazardous sharp wastes, injuries, and ...transmission of blood-borne pathogens.
This systematic review demonstrates and analyzes the current state of dissolvable antibacterial MN to establish their efficacy, and the effect of biomaterials selection on their final properties.
A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Three electronic databases Pubmed, Google scholar, and Scopus were explored for peer-reviewed articles. A total of 551 results with 176 citations and 915 references of resulted articles were reviewed and analyzed. No publication date restrictions were imposed. Last search was placed on 9th of June, 2021. The literature search in electronic databases according to the inclusion criteria was funneled down to 20 papers that were related to antibacterial effects of dissolving microneedles.
In conclusion, all included dissolving MN studies presented an enhanced or at least an equal antibacterial activity against common bacterial species when compared to conventional treatments. In addition, composition modifications can enhance their activity and performance. Other factors such as the size and geometry of the produced MN can be tailored to conform to the infected site's characteristics.
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Polymicrobial biofilms have been implicated in delayed wound healing, although the mechanisms by which biofilms impair wound healing are poorly understood. Many species of bacteria produce exotoxins ...and exoenzymes that may inhibit healing. In addition, oxygen consumption by biofilms may impede wound healing. In this study, we used oxygen microsensors to measure oxygen transects through in vitro-cultured biofilms, biofilms formed in vivo in a diabetic (db/db) mouse model, and ex vivo human chronic wound specimens. The results show that oxygen levels within both euthanized and live mouse wounds had steep gradients that reached minima ranging from 19 to 61% oxygen partial pressure, compared to atmospheric oxygen levels. The oxygen gradients in the mouse wounds were similar to those observed for clinical isolates cultured in vitro and for human ex vivo scabs. No oxygen gradients were observed for heat-killed scabs, suggesting that active metabolism by the viable bacteria contributed to the reduced oxygen partial pressure of the wounds. To characterize the metabolic activities of the bacteria in the mouse wounds, we performed transcriptomics analyses of Pseudomonas aeruginosa biofilms associated with the db/db mice wounds using Affymetrix microarrays. The results demonstrated that the bacteria expressed genes for metabolic activities associated with cell growth. Interestingly, the transcriptome results indicated that the bacteria within the wounds also experienced oxygen-limitation stress. Among the bacterial genes that were expressed in vivo were genes associated with the Anr-mediated hypoxia-stress response. Other bacterial stress response genes highly expressed in vivo were genes associated with stationary-phase growth, osmotic stress, and RpoH-mediated heat shock stress. Overall, the results support the hypothesis that the metabolic activities of bacteria in biofilms act as oxygen sinks in chronic wounds and that the depletion of oxygen contributes to the detrimental impact of biofilms on wound healing.
Bacterial extracellular DNA (eDNA) is important for the development of virtually all biofilms, their architecture, and their resistance to host defense. DNase I and DNase1L3 are important host immune ...strategies to prevent biofilm formation.eDNA in biofilms can adopt a Z-form, an alternative configuration of DNA that increases biofilm rigidity and is maintained by DNA-binding proteins. Z-DNA is resistant to DNase I, suggesting that bacteria have learned to circumvent certain host innate immune strategies by changing their eDNA physical form.DNA sensors cGAS/STING are involved in immune responses against Porphyromonas gingivalis biofilms in periodontitis and in the vicious cycle that maintains dysbiotic microbiota and chronic intestinal inflammation in IBD suggesting a role in recognizing eDNA in biofilms. eDNA-binding proteins are essential for biofilm integrity and eDNA/protein complexes are pathogen-associated molecular patterns (PAMPs) recognized by pattern recognition receptors (PRRs) like Toll-like receptors (TLRs).Many reports support the working hypothesis that eDNA is a universal biofilm-associated PAMP and that targeting eDNA might represent a novel therapeutic strategy against recurrent/chronic bacterial infections that generate biofilms.
Identifying the role of extracellular DNA in mammalian immune recognition of biofilms can improve our understanding of innate immune responses to bacterial infections; it may also help in the discovery of novel therapeutic targets against certain chronic/recurrent/antibiotic-resistant infections and autoimmunity.
Historically, the study of innate immune detection of bacterial infections has focused on the recognition of pathogen-associated molecular patterns (PAMPs) from bacteria growing as single cells in planktonic phase. However, over the past two decades, studies have highlighted an adaptive advantage of bacteria: the formation of biofilms. These structures are complex fortresses that stand against a hostile environment, including antibiotics and immune responses. Extracellular DNA (eDNA) is a crucial component of the matrix of most known biofilms. In this opinion article, I propose that eDNA is a universal PAMP that the immune system uses to recognize biofilms. Outstanding questions concern the discrimination between biofilm-associated eDNA and DNA from planktonic bacteria, the innate receptors involved, and the immune response to biofilms.
Historically, the study of innate immune detection of bacterial infections has focused on the recognition of pathogen-associated molecular patterns (PAMPs) from bacteria growing as single cells in planktonic phase. However, over the past two decades, studies have highlighted an adaptive advantage of bacteria: the formation of biofilms. These structures are complex fortresses that stand against a hostile environment, including antibiotics and immune responses. Extracellular DNA (eDNA) is a crucial component of the matrix of most known biofilms. In this opinion article, I propose that eDNA is a universal PAMP that the immune system uses to recognize biofilms. Outstanding questions concern the discrimination between biofilm-associated eDNA and DNA from planktonic bacteria, the innate receptors involved, and the immune response to biofilms.
Information processing in the mammalian brain relies on a careful regulation of the membrane potential dynamics of its constituent neurons, which propagates across the neuronal tissue via electrical ...signalling. We recently reported the existence of electrical signalling in a much simpler organism, the bacterium Bacillus subtilis. In dense bacterial communities known as biofilms, nutrient-deprived B. subtilis cells in the interior of the colony use electrical communication to transmit stress signals to the periphery, which interfere with the growth of peripheral cells and reduce nutrient consumption, thereby relieving stress from the interior. Here, we explicitly address the interplay between metabolism and electrophysiology in bacterial biofilms, by introducing a spatially extended mathematical model that combines the metabolic and electrical components of the phenomenon in a discretized reaction-diffusion scheme. The model is experimentally validated by environmental and genetic perturbations, and confirms that metabolic stress is transmitted through the bacterial population via a potassium wave. Interestingly, this behaviour is reminiscent of cortical spreading depression in the brain, characterized by a wave of electrical activity mediated by potassium diffusion that has been linked to various neurological disorders, calling for future studies on the evolutionary link between the two phenomena. This article is part of the theme issue 'Liquid brains, solid brains: How distributed cognitive architectures process information'.
Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses ...of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrated that unique flexible mechanical properties of SPCI enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess H2O2 present in infected tissues into O2, alleviating hypoxia and significantly boosting the antibacterial performance of phototherapy. Both in vitro and in vivo experiments confirmed that SPCI surpasses traditional rigid nanoplatforms in overcoming biofilm barriers, offering improved treatment outcomes for infections associated with bacterial biofilms. This study presents a viable strategy for managing bacterial biofilm-induced diseases by leveraging the unique attributes of a soft mesoporous organosilica-based nanoplatform.
This research introduces an innovative antimicrobial phototherapy soft nanoplatform that overcomes the inherent limitations posed by the protective barriers of bacterial biofilms. By soft nanoplatform with flexible mechanical properties, we enhance the penetration and delivery of photosensitizers into biofilms. The inclusion of catalase within this soft nanoplatform addresses the hypoxia in biofilms by converting hydrogen peroxide into oxygen in infected tissues, thereby amplifying the antibacterial effectiveness of phototherapy. Compared to traditional rigid nanoplatforms, this flexible nanoplatform not only promotes the delivery of therapeutic agents but also sets a new direction for treating bacterial biofilm infections, offering significant implications for future antimicrobial therapies.
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There is significant interest in modeling the mechanics and physics of growth of soft biological systems such as tumors and bacterial biofilms. Solid tumors account for more than 85% of cancer ...mortality and bacterial biofilms account for a significant part of all human microbial infections. These growing biological systems are a mixture of fluid and solid components and increase their mass by intake of diffusing species such as fluids and nutrients (swelling) and subsequent conversion of some of the diffusing species into solid material (growth). Experiments indicate that these systems swell by large amounts and that the swelling and growth are intrinsically coupled, with the swelling being an important driver of growth. However, many existing theories for swelling coupled growth employ linear poroelasticity, which is limited to small swelling deformations, and employ phenomenological prescriptions for the dependence of growth rate on concentration of diffusing species and the stress-state in the system. In particular, the termination of growth is enforced through the prescription of a critical concentration of diffusing species and a homeostatic stress. In contrast, by developing a fully coupled swelling-growth theory that accounts for large swelling through nonlinear poroelasticity, we show that the emergent driving stress for growth automatically captures all the above phenomena. Further, we show that for the soft growing systems considered here, the effects of the homeostatic stress and critical concentration can be encapsulated under a single notion of a critical swelling ratio. The applicability of the theory is shown by its ability to capture experimental observations of growing tumors and biofilms under various mechanical and diffusion–consumption constraints. Additionally, compared to generalized mixture theories, our theory is amenable to relatively easy numerical implementation with a minimal physically motivated parameter space.
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