Burn Wound Infection Research Articles

Bacterial Growth-Induced Tobramycin Smart Release Self-Healing Hydrogel for Pseudomonas aeruginosa-Infected Burn Wound Healing.

Burns are a common health problem worldwide and are highly susceptible to bacterial infections that are difficult to handle with ordinary wound dressings. Therefore, burn wound repair is extremely challenging in clinical practice. Herein, a series of self-healing hydrogels (QCS/OD/TOB/PPY@PDA) with good electrical conductivity and antioxidant activity were prepared on the basis of quaternized chitosan (QCS), oxidized dextran (OD), tobramycin (TOB), and polydopamine-coated polypyrrole nanowires (PPY@PDA NWs). These Schiff base cross-links between the aminoglycoside antibiotic TOB and OD enable TOB to be slowly released and responsive to pH. Interestingly, the acidic substances during the bacteria growth process can induce the on-demand release of TOB, avoiding the abuse of antibiotics. The antibacterial results showed that the QCS/OD/TOB/PPY@PDA9 hydrogel could kill high concentrations of Pseudomonas aeruginosa (PA), Staphylococcus aureus, and Escherichia coli in a short time and showed a bactericidal effect for up to 11 days in an agar plate diffusion experiment, while showing good in vivo antibacterial activity. Excellent and long-lasting antibacterial properties make it suitable for severely infected wounds. Furthermore, the incorporation of PPY@PDA endowed the hydrogel with near-infrared (NIR) irradiation assisted bactericidal activity of drug-resistant bacteria, conductivity, and antioxidant activity. Most importantly, in the PA-infected burn wound model, the QCS/OD/TOB/PPY@PDA9 hydrogel more effectively controlled wound inflammation levels and promoted collagen deposition, vascular generation, and earlier wound closure compared to Tegaderm dressings. Therefore, the TOB smart release hydrogels with on-demand delivery are extremely advantageous for bacterial-infected burn wound healing.

Antibacterial efficacy of lytic phages against multidrug-resistant Pseudomonas aeruginosa infections in bacteraemia mice models

BackgroundPseudomonas aeruginosa is an opportunistic pathogen that can cause a variety of infections in humans, such as burn wound infections and infections of the lungs, the bloodstream and surgical site infections. Nosocomial spread is often concurrent with high degrees of antibiotic resistance. Such resistant strains are difficult to treat, and in some cases, even reserved antibiotics are ineffective. A particularly promising therapy to combat infections of resistant bacteria is the deployment of bacteriophages, known as phage therapy. In this work, we evaluated the in vivo efficacy of two Pseudomonas phages in bacteremia mice models. For this study, non-neutropenic mice (BalB/C) were infected with P. aeruginosa AB030 strain and treated using two bacteriophages, AP025 and AP006.ResultsThe results showed that a single dose of phages at higher concentrations, bacteria: phage at 1:10 and 1:100 were effective in eliminating the bloodstream infection and achieving 100% mice survival.ConclusionThis study highlights the efficacy of using a single dose of phages to restore mice from bacteremia.

Topical Antimicrobial Agents for the Prevention of Burn-Wound Infection. What Do International Guidelines Recommend? A Systematic Review.

Choosing adequate topical antimicrobial agents in burn patientsstill representsa challenge.Therefore, thissystematic review was conducted tocompile and evaluatecurrent recommendations in international clinical practice guidelines (CPGs) to develop more consistent clinicalguidance. A systematicsearchfor CPGswas conducted independently by two reviewers using PubMed, EMBASE, Google Scholar, and external citations. The quality of theselectedCPGswas evaluatedseparatelyusing the AGREE II instrument, and intraclass correlation coefficients were calculated. Statistical analysis was performed using R V 1.4.1 statistical software. Eleven CPGs were included in the study.Most guidelines tend to recommendsilver-containingdressings over antiseptics or antibiotics,regardless of the depth of the burn.Silver sulfadiazine is the most recommended topical antimicrobial in low-resource settings.An overall mean appraisal AGREE II score of 68.2% wasobtained. The global intraclass correlation coefficient was 0.62 (95% confidence intervals 0.54-0.69), which corresponds to a substantial global concordance between both appraisers. Greatheterogeneity was found between recommendationsand CPGs. The three determining factors considered to issue a recommendation were the clinical scenario, burn-wound depth, and burn severity. There is consensus among the guidelines to use topical antimicrobials as a tool to prevent infection, and most of these recommend the use of silver-containing dressings for most scenarios. However, there is currently no ideal topical antimicrobial agent that can be recommended for all clinical scenarios.The development ofmoreconsistent recommendations iswarrantedto standardizeclinicalpractice.

Synergistic gentamicin-photodynamic therapy against resistant bacteria in burn wound infections

BackgroundMulti-resistant bacteria, partially a result of the abuse of antibiotics, have greatly diminished the effectiveness of antibiotics. The combination of antibiotics with other therapies like antimicrobial photodynamic therapy (aPDT) may provide a useful strategy for fighting resistant bacteria. Here, the synergistic bactericidal effects of toluidine blue (TB)-aPDT and gentamicin (GEN) were evaluated in vitro and in vivo. MethodsThe Post-antibacterial effects were measured at 600 nm (OD600) by a microplate reader. The bacterial envelope and biofilm were observed by a field emission scanning electron microscope. The expression of oxidative stress and Agr system-related genes was analyzed by qRT-PCR after GEN combined with TB-aPDT (GEN&aPDT). Besides, the burn infection model was established to investigate the cloning efficiency of immobilized bacteria, wound healing and inflammatory factors in the lesions. ResultsGEN&aPDT could inhibit the growth of Staphylococcus aureus (S. aureus) and multidrug-resistant S. aureus (MDR S. aureus) for up to 15 h, and destroyed the cell envelope and biofilm structure of S. aureus and MDR S. aureus. During the process, ROS played an important role, inducing oxidative stress and downregulating the expression of AgrA, AgrB and PSM in the Agr system, resulting in decreased bacterial virulence and infectivity. In addition, GEN&aPDT cotreatment could effectively promoted wound healing in burn-infected mice by reducing the numbers of bacterial colonization in the wound, decreasing the content of inflammatory factors, and increasing the expression of growth factors. ConclusionThe present study confirmed a bactericidal synergy between GEN and aPDT in vitro and in vivo, therein, the oxidative stress exhibited an important role in decreasing bacterial virulence and infectivity, which may bring new ideas for the treatment of bacterial resistance.

Antibacterial silk sericin/poly (vinyl alcohol) hydrogel with antifungal property for potential infected large burn wound healing: Systemic evaluation

Hydrogel-based burn wound dressings with excellent antibacterial, antifungal, and mechanical properties are ideal biomaterials to promote infected large burn wound healing. In this study, the hydrogel synthesized by repetitive freezing-thawing consists of poly (vinyl alcohol) (PVA), silk sericin (SS), and azithromycin (AZM), with genipin (GNP) as crosslinker. The FTIR showed that all hydrogel components were successfully blended. The swelling ratio, porosity, cell attachment, and proliferation improved with SS incorporation, while increased PVA content enhanced the mechanical performance of the hydrogel. The inclusion of AZM improved the antimicrobial property of the hydrogel towards Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The hydrogel showed sustained SS and AZM releases as well as cytocompatibility on keratinocytes and fibroblasts. Furthermore, the hydrogel displays skin adhesion ability when freeze-dried. In the in vivo study using an infected mouse full-thickness burn model with a 10% total body surface area, it was shown that burn injury led to increased inflammatory cytokine responses and macroscopic and microscopic alterations in the spleen and liver. The kidneys, on the other hand, revealed neither change. Interestingly, the prepared hydrogel had a better burn wound healing effect than the commercial Tegaderm™ film dressing, minimizing systemic burn effects. Hence, this novel hydrogel is projected to be a promising candidate for accelerated healing of infected burn wounds.

Silver Sulfadiazine: Action on Burn Wound Sepsis and Infections

The purpose of this systematic review and meta-review has shifted from assessing the consequences of silver sulfadiazine with most different drugs (SSD) for burn recovery and contamination prevention to different novel dressings, without or with silver. Burn units have to be able to better control sepsis. The degree to which a burn topical antibacterial agent is absorbed determines its effectiveness. Absorption of a topical antibacterial agent may be evaluated against the absorption of a test solute in isolated preparation of the stratum corneum in a cell in an in vitro model. Despite the fact that adding silver sulfadiazine (AgSu) to pure deoxyribonucleic acid (DNA) resulted in the formation of silver sulfadiazine (AgSu)the formation of AgSu-DNA complexes, no such complexes were detected in bacteria treated with AgSu. In treated bacteria, AgSu inhibited macromolecular syntheses as DNA synthesis was slightly more sensitive. A tiny amount of sulfadiazine appears to be active in this situation. Pediatric patients were randomly assigned to treatment with either Silva-Sorb® Gel or Silvadene® silver sulfadiazine cream for up to 21 days or to the point of full reepithelialization of the wound.
 Keyword: Silver, Sulfadiazine, Silvasorb, Bacteria, Burn, Wound.

Cyclic-di-GMP stimulates keratinocyte innate immune responses and attenuates methicillin-resistant Staphylococcus aureus colonization in a murine skin wound infection model

BackgroundStaphylococcus aureus is a leading cause for morbidity and mortality associated with skin and burn wound infections. Therapeutic options for methicillin-resistant S. aureus (MRSA) have dwindled and therefore alternative treatments are urgently needed. In this study, the immuno-stimulating and anti-MRSA effects of cyclic di-guanosine monophosphate (c-di-GMP), a uniquely bacterial second messenger and immuno-modulator, were investigated in HaCaT human epidermal keratinocytes and a murine skin wound infection model.ResultsStimulation of HaCaT cells with 125 μM c-di-GMP for 12 h prior to MRSA challenge resulted in a 20-fold reduction in bacterial colonization compared with untreated control cells, which was not the result of a direct c-di-GMP toxic effect, since bacterial viability was not affected by this dose in the absence of HaCaT cells. C-di-GMP-stimulated or MRSA-challenged HaCaT cells displayed enhanced secretion of the antimicrobial peptides human β-defensin 1 (hBD-1), hBD-2, hBD-3 and LL-37, but for hBD1 and LL-37 the responses were additive in a c-di-GMP-dose-dependent manner. Secretion of the chemokines CXCL1 and CXCL8 was also elevated after stimulation of HaCaT cells with lower c-di-GMP doses and peaked at a dose of 5 μM. Finally, pre-treatment of mice with a 200 nmol dose of c-di-GMP 24 h before a challenge with MRSA in skin wound infection model resulted in a major reduction (up to 1,100-fold by day 2) in bacterial CFU counts recovered from challenged skin tissue sections compared PBS-treated control animals. Tissue sections displayed inflammatory cell infiltration and enhanced neutrophil influx in the c-di-GMP pre-treated animals, which might account for the reduced ability of MRSA to colonize c-di-GMP pre-treated mice.ConclusionsThese results demonstrate that c-di-GMP is a potent immuno-modulator that can stimulate anti-MRSA immune responses in vivo and might therefore be a suitable alternative prophylactic or therapeutic agent for MRSA skin or burn wound infections.

Pseudomonas aeruginosa: Recent Advances in Vaccine Development.

Pseudomonas aeruginosa is an important opportunistic human pathogen. Using its arsenal of virulence factors and its intrinsic ability to adapt to new environments, P. aeruginosa causes a range of complicated acute and chronic infections in immunocompromised individuals. Of particular importance are burn wound infections, ventilator-associated pneumonia, and chronic infections in people with cystic fibrosis. Antibiotic resistance has rendered many of these infections challenging to treat and novel therapeutic strategies are limited. Multiple clinical studies using well-characterised virulence factors as vaccine antigens over the last 50 years have fallen short, resulting in no effective vaccination being available for clinical use. Nonetheless, progress has been made in preclinical research, namely, in the realms of antigen discovery, adjuvant use, and novel delivery systems. Herein, we briefly review the scope of P. aeruginosa clinical infections and its major important virulence factors.

Mutation to ispA Produces Stable Small-Colony Variants of Pseudomonas aeruginosa That Have Enhanced Aminoglycoside Resistance.

ABSTRACTPseudomonas aeruginosa is a major pathogen in burn wound infections. We present one of the first reports of small-colony variant (SCV) emergence of P. aeruginosa, taken from a patient under aminoglycosides for a persistent burn wound infection. We confirm the causative role of a single ispA mutation in SCV emergence and increased aminoglycoside resistance. IspA is involved in the synthesis of ubiquinone, providing a possible link between electron transport and SCV formation in P. aeruginosa.

Bio-functional hydrogel with antibacterial and anti-inflammatory dual properties to combat with burn wound infection.

Burn infection delays wound healing and increases the burn patient mortality. Consequently, a new dressing with antibacterial and anti-inflammatory dual properties is urgently required for wound healing. In this study, we propose a combination of methacrylate gelatin (GelMA) hydrogel system with silver nanoparticles embed in γ-cyclodextrin metal-organic frameworks (Ag@MOF) and hyaluronic acid-epigallocatechin gallate (HA-E) for the burn wound infection treatment. Ag@MOF is used as an antibacterial agent and epigallocatechin gallate (EGCG) has exhibited biological properties of anti-inflammation and antibacterial. The GelMA/HA-E/Ag@MOF hydrogel enjoys suitable physical properties and sustained release of Ag+. Meanwhile, the hydrogel has excellent biocompatibility and could promote macrophage polarization from M1 to M2. In vivo wound healing evaluations further demonstrate that the GelMA/HA-E/Ag@MOF hydrogel reduces the number of the bacterium efficiently, accelerates wound healing, promotes early angiogenesis, and regulates immune reaction. A further evaluation indicates that the noncanonical Wnt signal pathway is significantly activated in the GelMA/HA-E/Ag@MOF hydrogel treated group. In conclusion, the GelMA/HA-E/Ag@MOF hydrogel could serve as a promising multifunctional dressing for the burn wound healing.

Optimization, characterization and in vivo evaluation of mupirocin nanocrystals for topical administration

Treatment of infectious skin conditions resulting from wounds and burns with topical antibiotics is challenging, particularly those caused by methicillin-resistant Staphylococcus aureus bacteria (MRSA). This is due to the formation of bacterial biofilms characterized by antimicrobial resistance. Mupirocin (MP), a widely used topical antibiotic, is active against gram-positive bacteria including MRSA. However, MP suffers from sub-optimal therapeutic efficacy due to its poor water-solubility and the significant rise in MP-resistant S. aureus. In this study, the physico-chemical characteristics of MP were modified through nanocrystallization to improve its therapeutic efficacy for the treatment of skin infections. Mupirocin-nanocrystals (MP-NC) were prepared using a nanoprecipitation technique and optimized using a D-optimal response surface design. The optimization of MP-NC produced ultra-small monodisperse spherical particles with a mean diameter of 70 nm and a polydispersity index of 0.2. The design resulted in two optimal MP-NC formulations that were evaluated by performing series of in vitro, ex vivo, microbiological, and in vivo studies. In-vitro results showed a 10-fold increase in the saturation solubility and a 9-fold increase in the dissolution rate of MP-NC. Ex vivo permeation studies, using pig ears skin, showed a 2-fold increase in the dermal deposition of MP-NC with the highest drug deposition occurring at 500-µm skin depth. Moreover, the optimal MP-NC formulations were lyophilized and incorporated into a 2% w/w cream. Microbiological studies revealed a 16-fold decrease in the minimum inhibitory concentration and the minimum bactericidal concentration of MP-NC. In vivo studies, using a rat excision burn wound model, demonstrated rapid and complete healing of infected burn wounds in rats treated with MP-NC cream in comparison to marketed Avoban ointment. Our results suggest that nanocrystallization of MP may provide an avenue through which higher levels of a topically applied MP can be permeated into the skin to reach relevant infectious areas and exert potential local antibacterial effects.

Effect of Polycaprolactone Scaffold Containing Myrtus Communis Extract and Silver Nanoparticles on the Burn Wound Infection Induced by Methicillinresistant Staphylococcus Aureus in Rats

Background and Objectives: Regarding the important role of Staphylococcus aureus in burn wound infection, the present study aims to investigate of the effect of Polycaprolactone (PCL) scaffold containing Myrtus communis extract and silver nanoparticles on the healing of burn wound infections induced by Methicillin-Resistant Staphylococcus Aureus (MRSA) in rats. Methods: In this experimental study, 42 male Wistar rats were divided into seven groups of 6. After anesthesia, second-degree burns on the back of the rats’ necks were created and MRSA was then injected into the wound area. The rats’ wounds were treated daily with nanofiber PCL containing Myrtus communis extract and silver nanoparticles. Antimicrobial properties, wound healing percentage, wound area, malondialdehyde and nitric oxide levels, and total antioxidant capacity were measured. Data were analyzed in GraphPad software using Tukey’s test and ANOVA. Results: The wound area measurement showed the better effects on would healing in the groups treated by PCL+Myrtus communis extract and PCL+Myrtus communis extract+silver nanoparticles compared other groups. In bacteriological studies, the groups treated by PCL+Myrtus communis extract and PCL+Myrtus communis extract+silver nanoparticle showed more reduced bacterial growth compared to the PCL alone and positive control groups. Moreover, biochemical tests showed a decrease in malondialdehyde and nitric oxide levels in rats treated by PCL+Myrtus communis extract compared to other groups. Conclusion: Myrtus communis extract and silver nanoparticles can cause changes in PCL properties, which have an important role in reducing the time required for wound healing and in preventing the progression of MRSA-induced wound infection

Exploring the potential of benzoic acid derived from the endophytic fungus strain Neurospora crassa SSN01 as a promising antimicrobial agent in wound healing

Endophytic fungi are known to produce bioactive compounds with the potential to be used as promising drugs to treat a wide range of diseases. To the best of our knowledge, the use of bioactive metabolites derived from endophytic fungi, particularly against multidrug resistant (MDR) pathogens inhabiting burn wounds, has been emphasized for the first time. Therefore, the purpose of this study is to investigate the potential of purified benzoic acid (BA) derived from Neurospora crassa, an endophytic fungus isolated from Lycium shawii, as a promising and alternative safe antimicrobial candidate in wound healing. As a result, benzoic acid, a safe and nontoxic compound, may be a promising candidate for combating clinical MDR pathogens of burn wound infections. In this study, Neurospora crassa strain SSN01 (MW856826) was successfully identified for the first time as a new BA-producing endophytic fungus isolated from Lycium shawii. The concentration of BA in the ethyl acetate extract reached 244 mg/mL. Purified BA had a detrimental effect on the MDR strains tested, and the MDR Staphylococcus aureus strain SA-17 was clearly more susceptible to BA as compared to the other tested MDR bacterial and fungal strains. Toxicological studies on experimental animals were conducted to evaluate the toxicity of BA and a suitable dose regimen for future human use. Oral administration of BA at the highest concentration of 300 µg/kg body weight resulted in nontoxic signs and no mortality. In vivo histopathological examination revealed that BA, as a nontoxic and safe compound, could be a promising candidate for wound healing, combating MDR pathogens of burn wound infections.

Photo-Crosslinked Antimicrobial Hydrogel Exhibiting Wound Healing Ability and Curing Infections In Vivo.

With the increasing focus on healthcare research in the current times, therapeutic and biomaterial interventions for healing of wounds and mitigation of wound-associated infections have seen expedited progress. Conventional approaches consist of release-active gels, which demonstrate leaching of antimicrobials, such as antibiotics, metal ions, etc. However, these systems suffer from the disadvantages of burst release, reservoir exhaustion, and associated toxicity. In this report, intrinsically antimicrobial hydrogel (HyDex) is developed by one-pot UV crosslinking of methacrylated dextran, polyethylene glycol diacrylate, and cationic lipophilic methacrylate with varied hydrophobic chain, which displays broad-spectrum antimicrobial activity, hemostatic ability, and rapid wound closure efficacy. The optimized hydrogel exhibits potent antimicrobial efficacy against multidrug-resistant Gram-positive and Gram-negative bacteria as well as against pathogenic fungus Candida albicans. The HyDex hydrogel shows rapid arrest of bleeding in mice liver puncture model. The hydrogel kills carbapenem-resistant Acinetobacter baumannii in a murine model of burn wound infection with >99% reduction in bacterial burden. Furthermore, this hydrogel displays significant reduction in inflammatory responses, with accelerated wound healing in rat deep wound model. Collectively, these results imply the excellent promise held by lead hydrogel to be developed for tackling deep tissue wounds, notorious infections, and resulting inflammatory responses.

Characterization of Distinct Biofilm Cell Subpopulations and Implications in Quorum Sensing and Antibiotic Resistance.

ABSTRACTBacteria change phenotypically in response to their environment. Free swimming cells transition to biofilm communities that promote cellular cooperativity and resistance to stressors and antibiotics. We uncovered three subpopulations of cells with diverse phenotypes from a single-species Pseudomonas aeruginosa PA14 biofilm, and used a series of steps to isolate, characterize, and map these cell subpopulations in a biofilm. The subpopulations were distinguishable by size and morphology using dynamic light scattering (DLS) and scanning electron microscopy (SEM). Additionally, growth and dispersal of biofilms originating from each cell subpopulation exhibited contrasting responses to antibiotic challenge. Cell subpopulation surface charges were distinctly different, which led us to examine the ionizable surface molecules associated with each subpopulation using mass spectrometry. Matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of cell subpopulations revealed ions unique to each subpopulation of cells that significantly co-localized with ions associated with quorum sensing. Transcript levels of algR, lasR, and rhlI in subpopulations isolated from biofilms differed from levels in planktonic stationary and mid-log cell subpopulations. These studies provide insight into diverse phenotypes, morphologies, and biochemistries of PA14 cell subpopulations for potential applications in combating bacterial pathogenesis, with medical, industrial, and environmental complications.

Exploring the therapeutic potential of acetonic plant extracts in the healing of skin wounds infected with multidrug resistant pathogens.

Open wounds are easily susceptible to infection by multi-drug resistant (MDR) pathogens. The emergence of MDR super bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus spp, fungi such as Aspergillus niger and Candida spp, has been identified to significantly increase the incidence rate. Therefore, it is necessary to develop a suitable barrier to prevent infection and enhance wound healing. On the other hand, medicinal plants could represent a significant source of new antimicrobial drugs for combating MDR pathogens. Out of 60 clinical skin burn cases, 51 patients (85%) had polymicrobial infections, while the remaining had monomicrobial infections. Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumonia were identified as the most common bacterial isolates based on morphological and biochemical tests. However, Candida albicans, Candida parasitosis, Candida glabrata, Candida famata, Aspergillus niger, and Exophilia spinifera were the most common fungal isolates found in skin burn cases. MDR classification was reported in 21 of the 39 bacterial isolates and 8 of the 27 fungal isolates. The antimicrobial activity of tested acetonic plant extracts rosemary, henna, and licorice against MDR isolates was compared to the commercial antibiotic agents. Acetonic rosemary extract outperformed henna and licorice extracts in antibacterial activity, while licorice extract outperformed henna and rosemary extracts on antifungal activity. As a result, rosemary and licorice extracts were chosen to prepare a topical cream for further in vivo wound healing and histopathology. Based on the antimicrobial potential of acetonic plant extracts against MDR isolates, BI-41 and FI-17 were chosen for in vivo wound healing. BI-41 stands for the molecularly identified species Pseudomonas aeruginosa SSM-15, while FI-17 stands for molecularly identified species Aspergillus niger SSM-27. In vivo testing showed that both cream formulas had excellent healing properties when administered topically. In vivo histopathological examination revealed that acetonic rosemary and licorice extract could be promising for wound healing, combating MDR pathogens of burn wound infections.

Light-activated molecular machines are fast-acting broad-spectrum antibacterials that target the membrane.

The increasing occurrence of antibiotic-resistant bacteria and the dwindling antibiotic research and development pipeline have created a pressing global health crisis. Here, we report the discovery of a distinctive antibacterial therapy that uses visible (405 nanometers) light-activated synthetic molecular machines (MMs) to kill Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, in minutes, vastly outpacing conventional antibiotics. MMs also rapidly eliminate persister cells and established bacterial biofilms. The antibacterial mode of action of MMs involves physical disruption of the membrane. In addition, by permeabilizing the membrane, MMs at sublethal doses potentiate the action of conventional antibiotics. Repeated exposure to antibacterial MMs is not accompanied by resistance development. Finally, therapeutic doses of MMs mitigate mortality associated with bacterial infection in an in vivo model of burn wound infection. Visible light–activated MMs represent an unconventional antibacterial mode of action by mechanical disruption at the molecular scale, not existent in nature and to which resistance development is unlikely.

RETRACTED ARTICLE: Burn Wounds: Proliferating Site for Biofilm Infection.

Burn wounds can create significant damage to human skin, compromising one of the key barriers to infection. The leading cause of death among burn wound patients is infection. Even in the patients that survive, infections can be notoriously difficult to treat and can cause lasting damage, with delayed healing and prolonged hospital stays. Biofilm formation in the burn wound site is a major contributing factor to the failure of burn treatment regimens and mortality as a result of burn wound infection. Bacteria forming a biofilm or a bacterial community encased in a polysaccharide matrix are more resistant to disinfection, the rigors of the host immune system, and, critically, more tolerant to antibiotics. Burn wound-associated biofilms are also thought to act as a launchpad for bacteria to establish deeper, systemic infection, and ultimately bacteremia and sepsis. In this review, we discuss some of the leading burn wound pathogens and outline how they regulate biofilm formation in the burn wound microenvironment. We also discuss the new and emerging models that are available to study burn wound biofilm formation in vivo.

Antibacterial activity of chitosan-based nanohybrid membranes against drug-resistant bacterial isolates from burn wound infections

Biocompatible and non-toxic properties of chitosan make it a candidate with excellent application prospects in developing wound dressing conjugate compounds. Six different chitosan-based nanohybrid membranes were evaluated against multidrug-resistant bacterial isolates. Different combinations of chitosan, ciprofloxacin (CIP), biofunctionalized montmorillonite (MMT), and montmorillonite with sulfate chains (SMMT) were provided, and their antibacterial activity was assessed using the colony count method. Totally, 27 drug-resistant isolates, including 6x methicillin-resistant Staphylococcus aureus, 7 vancomycin-resistant Enterococcus faecalis, 4 Acinetobacter baumannii, and 10 Pseudomonas aeruginosa isolates were identified from burn wound infections. Chitosan and montmorillonite did not show significant antibacterial effect (p > 0.05), but chitosan/SMMT/CIP was the most effective nanocomposite (p < 0.01). Chitosan-based nanocomposites with ciprofloxacin could effectively reduce the susceptibility of drug-resistant bacterial isolates. Bacterial targeting using nanosystems provides an opportunity for effective antibiotic treatment by improving antibacterial efficacy.

Rational inhibitor design for Pseudomonas aeruginosa salicylate adenylation enzyme PchD

Pseudomonas aeruginosa is an increasingly antibiotic-resistant pathogen that causes severe lung infections, burn wound infections, and diabetic foot infections. P. aeruginosa produces the siderophore pyochelin through the use of a non-ribosomal peptide synthetase (NRPS) biosynthetic pathway. Targeting members of siderophore NRPS proteins is one avenue currently under investigation for the development of new antibiotics against antibiotic-resistant organisms. Here, the crystal structure of the pyochelin adenylation domain PchD is reported. The structure was solved to 2.11 Å when co-crystallized with the adenylation inhibitor 5′-O-(N-salicylsulfamoyl)adenosine (salicyl-AMS) and to 1.69 Å with a modified version of salicyl-AMS designed to target an active site cysteine (4-cyano-salicyl-AMS). In the structures, PchD adopts the adenylation conformation, similar to that reported for AB3403 from Acinetobacter baumannii.Graphical abstract