Engineering Ag-Decorated Graphene Oxide Nano-Photothermal Platforms with Enhanced Antibacterial Properties for Promoting Infectious Wound Healing.

Introduction: Graphene oxide (GO) nanoparticles have emerged as a compelling photothermal agent (PHTA) in the realm of photothermal antibacterial therapy, owing to their cost-effectiveness, facile synthesis, and remarkable photostability. Nevertheless, the therapeutic efficacy of GO nanoparticles is commonly hindered by their inherent drawback of low photothermal conversion efficiency (PCE). Methods: Herein, we engineer the Ag/GO-GelMA platform by growing the Ag on the surface of GO and encapsulating the Ag/GO nanoparticles into the GelMA hydrogels. Results: The resulting Ag/GO-GelMA platform demonstrates a significantly enhanced PCE (47.6%), surpassing that of pure GO (11.8%) by more than fourfold. As expected, the Ag/GO-GelMA platform, which was designed to integrate the benefits of Ag/GO nanoparticles (high PCE) and hydrogel (slowly releasing Ag+ to exert an inherent antibacterial effect), has been shown to exhibit exceptional antibacterial efficacy. Furthermore, transcriptome analyses demonstrated that the Ag/GO-GelMA platform could significantly down-regulate pathways linked to inflammation (the MAPK and PI3K-Akt pathways) and had the ability to promote cell migration. Discussion: Taken together, this study presents the design of a potent photothermal antibacterial platform (Ag/GO-GelMA) aimed at enhancing the healing of infectious wounds. The platform utilizes a handy method to enhance the PCE of GO, thereby making notable progress in the utilization of GO nano-PHTAs.

Detection of Pseudomonas aeruginosa pus wound isolate using a polymerase chain reaction targeting 16S rRNA and gyrB genes: A case from Indonesia.

Infectious wounds on the skin surface are easily colonized by bacteria from pyogenic group that manifest as inflammation, such as Pseudomonas aeruginosa. P. aeruginosa is a Gram-negative bacterium and an opportunistic pathogen known for causing invasive state in critically ill and immunocompromised patients. The aim of this study was to detect the 16S rRNA and gyrB genes in P. aeruginosa using polymerase chain reaction (PCR) method. The sample in this study was pus isolate from a 5-year-old boy with leg wounds. The bacteria were isolated on brain heart infusion broth (BHIB) media and identified with molecular identification. Sequencing and BLAST analysis were carried out to determine the similarity of gene identity by comparing sample sequence with other isolate sequences on the Gene Bank. The results of molecular identification showed amplification DNA band of around 934 base pairs (bp) for 16S rRNA and 225 bp for gyrB gene. The BLAST program demonstrated that the sample had 99.89% similarity with P. aeruginosa strain XC4 (accession code ON795960.1) for the 16S rRNA gene. Meanwhile, the gyrB gene exhibited 99.10% similarity with the P. aeruginosa strain PSA-1.2 (accession code KP172300.1).

Human breast milk isolated lactic acid bacteria: antimicrobial and immunomodulatory activity on the Galleria mellonella burn wound model.

Introduction: Managing burn injuries is a challenge in healthcare. Due to the alarming increase in antibiotic resistance, new prophylactic and therapeutic strategies are being sought. This study aimed to evaluate the potential of live Lactic Acid Bacteria for managing burn infections, using Galleria mellonella larvae as an alternative preclinical animal model and comparing the outcomes with a common antibiotic. Methods: The antimicrobial activity of LAB isolated from human breast milk was assessed in vitro against Pseudomonas aeruginosa ATCC 27853. Additionally, the immunomodulatory effects of LAB were evaluated in vivo using the G. mellonella burn wound infection model. Results and discussion: In vitro results demonstrated the antimicrobial activity of Lactic Acid Bacteria against P. aeruginosa. In vivo results show that their prophylactic treatment improves, statistically significant, larval survival and modulates the expression of immunity-related genes, Gallerimycin and Relish/NF-κB, strain-dependently. These findings lay the foundation and suggest a promising alternative for burn wound prevention and management, reducing the risk of antibiotic resistance, enhancing immune modulation, and validating the potential G. mellonella as a skin burn wound model.

Antimicrobial spectrum against wound pathogens and cytotoxicity of star-arranged poly-l-lysine-based antimicrobial peptide polymers.

Introduction. As growing numbers of patients are at higher risk of infection, novel topical broad-spectrum antimicrobials are urgently required for wound infection management. Robust pre-clinical studies should support the development of such novel antimicrobials.Gap statement. To date, evidence of robust investigation of the cytotoxicity and antimicrobial spectrum of activity of antimicrobial peptides (AMP)s is lacking in published literature. Using a more clinical lens, we address this gap in experimental approach, building on our experience with poly-l-lysine (PLL)-based AMP polymers.Aim. To evaluate the in vitro bactericidal activity and cytotoxicity of a PLL-based 16-armed star AMP polymer, designated 16-PLL10, as a novel candidate antimicrobial.Methods. Antimicrobial susceptibilities of clinical isolates and reference strains of ESKAPE (Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp.) pathogens, to 16-PLL10 were investigated. Human erythrocyte haemolysis and keratinocyte viability assays were used to assess toxicity. Modifications were made to 16-PLL10 and re-evaluated for improvement.Results. Minimum bactericidal concentration of 16-PLL10 ranged from 1.25 µM to ≥25 µM. At 2.5 µM, 16-PLL10 was broadly bactericidal against ESKAPE strains/wound isolates. Log-reduction in colony forming units (c.f.u.) per millilitre after 1 h, ranged from 0.3 (E. cloacae) to 5.6 (K. pneumoniae). At bactericidal concentrations, 16-PLL10 was toxic to human keratinocyte and erythrocytes. Conjugates of 16-PLL10, Trifluoroacetylated (TFA)-16-PLL10, and Poly-ethylene glycol (PEG)ylated 16-PLL10, synthesised to address toxicity, only moderately reduced cytotoxicity and haemolysis.Conclusions. Due to poor selectivity indices, further development of 16-PLL10 is unlikely warranted. However, considering the unmet need for novel topical antimicrobials, the ease of AMP polymer synthesises/modification is attractive. To support more rational development, prioritising clinically relevant pathogens and human cells, to establish selective toxicity profiles in vitro, is critical. Further characterisation and discovery utilising artificial intelligence and computational screening approaches can accelerate future AMP nanomaterial development.

Examining the prevalence and antimicrobial resistance profiles of multidrug-resistant bacterial isolates in wound infections from Indonesian patients.

The emergence of multidrug-resistant (MDR) infections in wounds is a significant public health issue. The aim of this study was to investigate the prevalence and antimicrobial resistance profiles of MDR bacterial isolates in wound infections. Through a cross-sectional study, 1,035 bacterial isolates were collected from wound infection patients at Tugurejo Hospital in Semarang, Indonesia, over a three-year period (from January 2020 to December 2022). Initial identification involved Gram staining and colony morphology assessment, followed by biochemical assays and antimicrobial susceptibility testing using the VITEK®2 Compact system. Gram-negative bacteria constituted the majority of isolates (60.77%, n=629). The predominant strains included were Staphylococcus spp. (30.92%, n=320), Escherichia coli (18.45%, n=191), and Klebsiella pneumoniae (13.04%, n=135). Notably, Gram-negative bacteria exhibited a significantly higher likelihood of MDR development compared to their Gram-positive counterparts (p<0.001), with Gram-negative bacteria having a 2.05 times higher probability of acquiring MDR. These findings underscore the urgent need for comprehensive surveillance of antimicrobial resistance patterns and the implementation of tailored antimicrobial stewardship programs to address the pressing public health challenge of MDR wound infections. Further research is warranted to elucidate the complex interplay of factors contributing to MDR development in wound infections, thereby informing targeted intervention strategies and improving patient outcomes.

Enhanced exploration of the mode of action of a five-layer foam dressing: critical properties to support wound healing.

OBJECTIVE: The aim of this in vitro experimental series was to explore the mode of action of a hydrocellular polyurethane foam dressing (HPFD) and how its advanced features support beneficial interactions with the wound bed to address common barriers to wound healing, thus supporting improved clinical outcomes. METHOD: Multiple in vitro microbiological tests were performed, assessing prevention of bacterial ingress, surface removal of bacteria, bacterial sequestration and retention into the dressing in a clinically relevant environment. Odour molecule concentrations were measured using gas chromatography and further assays explored matrix metalloproteinase (MMP)-9 retention in the dressing using enzyme linked immunosorbent assay. RESULTS: The HPFD demonstrated marked reductions in bioburden levels across multiple tests. These included prevention of bacterial ingress for seven days, removal of surface bacteria and absorption into the dressing. Further tests identified that most bacteria were sequestered into the hyperabsorbent layer (90.5% for Pseudomonas aeruginosa and 89.6% for meticillin-resistant Staphylococcus aureus). Moreover, the majority of bacteria (99.99% for both test organisms) were retained within the dressing, even upon compression. Additional tests demonstrated a marked reduction of odour molecules following incubation with HPFD and total retention of protease MMP-9 within the dressing. CONCLUSIONS: Proactive management of the wound environment with an appropriate advanced wound dressing, such as the HPFD examined in these in vitro investigations, can not only help to minimise the barriers to healing, as observed across this test series by direct interaction with the wound bed, but may, as a result, provide an ideal environment for wound progression with minimal disturbance.

Systematic review and meta-analysis of diagnostic test accuracy in chronic wound's microbiology.

PURPOSE: This study aims to assess the diagnostic accuracy of non-culture-based methodologies for detecting microorganisms in chronic wounds. METHODS: We systematically reviewed studies that evaluated the diagnostic accuracy of alternative tests in chronic wound samples, excluding studies focused on animal samples or unrelated conditions. The search encompassed PubMed, CINAHL, Scopus and Web of Science databases, employing the QUADAS-2 tool for risk of bias assessment. Our search included the PubMed, CINAHL, Scopus and Web of Science databases, and we assessed the risk of bias using the QUADAS-2 tool. A meta-analysis was conducted on polymerase chain reaction (PCR) and colorimetric methods to determine sensitivity, specificity, diagnostic odds ratio, and summary receiver-operating characteristic (sROC) curves using a random-effects model. For methods not suitable for quantitative synthesis, a narrative synthesis was performed. RESULTS: Nineteen studies involving various types of chronic wounds were analysed, revealing diverse diagnostic methods including fluorescence, PCR, colorimetry, voltammetry, electronic nose, biosensors, enzymatic methods, staining and microscopy. Combining fluorescence with clinical signs and symptoms (CSS) versus culture showed significant accuracy. Colorimetry demonstrated low sensitivity but high specificity, with a diagnostic odds ratio of 6.3. PCR generally exhibited good accuracy, although significant heterogeneity was noted, even in subgroup analyses. CONCLUSIONS: This study identified a broad spectrum of diagnostic approaches, highlighting the superior diagnostic accuracy achieved when microbiological analysis is combined with clinical assessments. However, the heterogeneity and methodological variations across studies present challenges in meta-analysis. Future research should aim for standardized and homogeneous study designs to enhance the assessment of diagnostic accuracy for alternative methods.

Ferrous sulfate remodels the properties of sodium alginate-based hydrogel and facilitates the healing of wound infection caused by MRSA.

Frequent occurrence of wound infection caused by multiple-resistant bacteria (MRB) has posed a serious challenge to the current healthcare system relying on antibiotics. The development of novel antimicrobial materials with high safety and efficacy to heal wound infection is of great importance in combating this crisis. Herein, we prepared a promising antibacterial hydrogel by cross-linking ferrous ions (Fe2+) with the deprotonated carboxyl anion in sodium alginate (Na-ALG) to cure wound infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, ferrous-modified Na-ALG (Fe-ALG) hydrogel demonstrated better properties compared to the traditional Na-ALG-based hydrogels, including injectability, self-healing, appropriate fluidity, high-water retention, potent MRSA-killing efficacy, and excellent biocompatibility. Importantly, the addition of Fe2+ enhances the antibacterial efficacy of the Na-ALG hydrogel, enabling it to effectively eliminate MRSA and accelerate the healing of antibiotic-resistant bacterial-infected wounds in a remarkably short period (10 days). This modification not only facilitates wound closure and fur generation, but also mitigates systemic inflammation, thereby effectively impeding the spread of MRSA to the lungs. Taken together, Fe-ALG hydrogel is a promising therapeutic material for treating wound infections by Staphylococcus aureus, especially by antibiotic-resistant strains like MRSA.

Chitosan/agarose hydrogel dressing: pH response real-time monitoring and chemo-/photodynamic therapy synergistic treatment of infected wounds.

The early diagnosis and real-time monitoring of bacterial infections are of great significance for the establishment of integrated diagnosis and treatment systems. In this study, a pH-responsive smart hydrogel patch system, named CABP, was developed to monitor and treat wound infections. CABP has a sandwich structure, with non-woven fabric/chitosan (NF/CS) as the intermediate skeleton layer, Agarose/chitosan/Bromothymol Blue (AG/CS/BTB) hydrogel as the detection layer, and Agarose/chitosan/phthalocyanine (AG/CS/Pc) hydrogel as the treatment layer. When Staphylococcus aureus (S. aureus) infection occurs, the pH of the environment decreases, which triggers the CABP to change from its original blue color to yellow, achieving an intuitive visual transformation. Moreover, the hydrogel patch showed a significant inhibition rate of up to 99.99971 % against S. aureus under 660 nm light radiation, showing a good photodynamic therapy (PDT)/ chemotherapy (CT) synergistic effect. In addition, CABP showed excellent antibacterial and wound healing effects on S. aureus infection in a full-layer skin defect experiment. In short, the patch system is simple to prepare and easy to use, and can provide important research value for the integrated diagnosis and treatment system in biomedical applications.

Cuttlefish ink-derived melanin nanoparticle-embedded tremella fuciformis polysaccharide hydrogels for the treatment of MRSA-infected diabetic wounds.

Diabetic wounds arise great attention as they are difficult to heal and easily suffer from serious bacterial infection. However, the overuse of antibiotics increases the resistance of bacteria and makes common drugs ineffective. Here, we developed a photothermal hydrogel (TFP/NP) composed of tremella fuciformis polysaccharides (TFPs) and cuttlefish ink-derived melanin nanoparticles (NPs). The NPs can produce reliable photothermal effects under near-infrared laser (NIR) irradiation and help to remove the bacteria in the wounds, while TFPs were able to form hydrogel frameworks which possessed anti-inflammatory effects and could be applied to promote wound healing. The TFP/NP hydrogels produced stable thermal effects under NIR irradiation and could continuously kill bacteria. The experiment on a full-layer skin wound sMRSA activity and could improve the healing efficiency. The wounds of the mice could be repaired within 14 days after reasonable treatment. In addition, the hydrogels play significant roles in promoting collagen deposition, anti-inflammation, angiogenesis, and cell proliferation during the therapeutic process. This research provides a simple and effective method for the therapy of bacterial infection wounds through the synergistic effect of TFPs and NPs.

High Therapeutic Index α-Helical AMPs and Their Therapeutic Potential on Bacterial Lung and Skin Wound Infections.

Antimicrobial peptides (AMPs) possess strong antibacterial activity and low drug resistance, making them ideal candidates for bactericidal drugs for addressing the issue of traditional antibiotic resistance. In this study, a template (G(XXKK)nI, G = Gly; X = Leu, Ile, Phe, or Trp; n = 2, 3, or 4; K = Lys; I = Ile.) was employed for the devised of a variety of novel α-helical AMPs with a high therapeutic index. The AMP with the highest therapeutic index, WK2, was ultimately chosen following a thorough screening process. It demonstrates broad-spectrum and potent activity against both standard and multidrug-resistant bacteria, while also showing low hemolysis and rapid and efficient time-kill kinetics. Additionally, WK2 exhibits excellent efficacy in treating mouse models of Klebsiella pneumonia-induced lung infections and methicillin-resistant Staphylococcus aureus (MRSA)-induced skin wound infections while demonstrating good safety profiles in vivo. In conclusion, the template-based design methodology for novel AMPs with high therapeutic indices offers new insights into addressing antibiotic resistance problems. WK2 represents a promising antimicrobial agent.

Oligolysine-based hydrogel dressing with antibacterial, anti-inflammatory, and tissue-adhesion activities for infected wound treatment.

Fabricating injectable hydrogel with multiple functions and effective promotion of wound repair has a great prospect in treatment of bacterial infected wounds. Herein, a pH/reactive oxygen species (ROS) dual responsive injectable hydrogel (PVBDL-gel) was constructed, the PVBDL-gel was cross-linked by dynamic Schiff base bonds and borate ester bonds between poly(vanillin acrylate-co-3 acrylamide phenylboronic acid-co-N,N-dimethylacrylamide) (P(VA-co-AAPBA-co-DMA)), oligolysines and polyvinyl alcohol (PVA). The anti-inflammatory drug, dexamethasone sodium phosphate (DEX), was encapsulated in this hydrogel. The hydrogel exhibited excellent degradability, stable rheology and suitable tissue adhesion, more importantly, which showing pH/ROS responsive ability and controllable releasing of DEX. In vitro and in vivo experiment results showed that the PVBDL-gel with good biocompatibility and efficient anti-infection ability can effectively eradicate 99.9 % of pathogenic bacteria within 3 h and promote the repair and regeneration of bacterial infection wounds. This novel multifunctional injectable hydrogel has great application in the field of bacterial infection wound repair.

Antibiofilm and wound healing efficacy of rhamnolipid biosurfactant against pathogenic bacterium Staphylococcus aureus.

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.

Concanavalin-conjugated zinc-metal-organic framework drug for pH-controlled and targeted therapy of wound bacterial infection.

Wounds are prone to infection which may be fatal to the life of the patient. The use of antibiotics is essential for managing bacterial infections in wounds, but the long-term use of high doses of antibiotics may lead to bacterial drug resistance and even to creation of superbacteria. Therefore, the development of targeted antimicrobial treatment strategies and the reduction in antibiotic usage are of utmost urgency. In this study, a multifunctional nanodrug delivery system (Cef-rhEGF@ZIF-8@ConA) for the treatment of bacteriostatic infection was synthesized through self-assembly of Zn2+, cefradine (Cef) and recombinant human epidermal growth factor (rhEGF), then conjugated with concanavalin (ConA), which undergoes pH-responsive degradation to release the drugs. First, ConA can specifically combine with bacteria and inhibit the rapid release of Zn2+ ions, thus achieving a long-acting antibacterial effect. Cef exerts its antibacterial effect by inhibiting the synthesis of bacterial membrane proteins. Finally, Zn2+ ions released from the Zn-metal-organic framework (MOF) demonstrate bacteriostatic properties by enhancing the permeability of the bacterial cell membrane. Furthermore, rhEGF upregulates angiogenesis-associated genes, thereby promoting angiogenesis, re-epithelialization and wound healing processes. The results showed that Cef-rhEGF@ZIF-8@ConA has good biocompatibility, with antibacterial efficacy against Staphylococcus aureus and Escherichia coli of 99.61 % and 99.75 %, respectively. These nanomaterials can inhibit the release of inflammatory cytokines and promote the release of anti-inflammatory cytokines, while also stimulating the proliferation of fibroblasts to facilitate wound healing. Taken together, the Cef-rhEGF@ZIF-8@ConA nanosystem is an excellent candidate in clinical therapeutics for bacteriostatic infection and wound healing.

Accelerated healing of intractable biofilm-infected diabetic wounds by trypsin-loaded quaternized chitosan hydrogels that disrupt extracellular polymeric substances and eradicate bacteria.

Complex and stubborn bacterial biofilm infections significantly hinder diabetic wound healing and threaten public health. Therefore, a dressing material that effectively clears biofilms and promotes wound healing is urgently required. Herein, we introduce a novel strategy for simultaneously dispersing extracellular polymeric substances and eradicating drug-resistant bacteria. We prepared an ultrabroad-spectrum and injectable quaternized chitosan (QCS) hydrogel loaded with trypsin, which degrades biofilm extracellular proteins. Increased temperature initiated QCS gelation to form the hydrogel, enabling the sustained release of trypsin and effective adherence of the hydrogel to irregularly shaped wounds. To reproduce clinical scenarios, biofilms formed by a mixture of Staphylococcus aureus (S. aureus), Methicillin-resistant S. aureus, and Pseudomonas aeruginosa were administered to the wounds of rats with streptozotocin-induced diabetes. Under these severe infection conditions, the hydrogel efficiently suppressed inflammation, promoted angiogenesis, and enhanced collagen deposition, resulting in accelerated healing of diabetic wounds. Notably, the hydrogel demonstrates excellent biocompatibility without cytotoxicity. In summary, we present a trypsin-loaded QCS hydrogel with tremendous clinical applications potential for the treatment of chronic infected wounds.

Double-network polyphenol chitosan hydrogels with instant aldehyde-ß-cyclodextrin-based structure as potential for treating bacterially infected wounds.

Treatment of multiple bacterial infected wounds by eliminating bacteria and promoting tissue regeneration remains a clinical challenge. Herein, dual-network hydrogels (CS-GA/A-ß-CD) with snap-structure were designed to achieve curcumin immobilization, using gallic acid-grafted chitosan (CS-GA) and aldehyde-ß-cyclodextrin (A-ß-CD) crosslinked. A-ß-CD were able to achieve rapid dissolution (≥222.35 mg/mL H2O), and helped CS-GA/A-ß-CD achieve rapid gelation (≤66.23 s). By adjusting the ratio of aldehyde groups of A-ß-CD, mechanical properties and drug release can be controlled. CS-GA/A-ß-CD/Cur exhibited excellent antimicrobial properties against S. aureus, E. coli, and P. aeruginosa. In vivo experiments demonstrated that CS-GA/A-ß-CD/Cur achieved acute bacterial infection wound healing after 20th days, proving its great potential for wound dressing.

Treatment of bacterially contaminated lower extremity ulcers with a fatty acid-containing wound matrix: a case series.

OBJECTIVE: The aim was to evaluate the effectiveness of a marine omega fatty acid-containing multimodal wound matrix (MWM) in reducing bacterial contamination and supporting wound area reduction (WAR) in patients with hard-to-heal wounds of varying aetiologies. METHOD: A prospective, single-site, pilot case series of patients with hard-to-heal wounds. All wounds were considered non-healing prior to inclusion as they had failed to achieve at least 50% WAR after at least four weeks of standard of care (SoC) treatments. Patients were seen once weekly for wound assessments, matrix application and dressing changes. Baseline and weekly fluorescence images, standard wound images and wound measurements were obtained. RESULTS: A total of three patients, two with venous leg ulcers (VLUs) and one with a diabetic foot ulcer (DFU) were enrolled in this pilot study. The mean baseline wound age prior to study enrolment was 24 weeks, with a mean baseline wound size of 8.61cm2. The two VLUs went on to complete closure. The DFU displayed a total WAR of 53% by six weeks, when the patient was lost to follow-up due to a geographical relocation. The mean percentage area reduction of all wounds combined was 82% upon study completion. CONCLUSION: The use of MWM proved to be effective and safe in this patient cohort. The wounds included in this case series failed to enter a healing trajectory with SoC wound therapies. The MWM supported wound closure and reduced bacterial loads in this patient cohort.

Peptide clustering enhances large-scale analyses and reveals proteolytic signatures in mass spectrometry data.

Recent advances in mass spectrometry-based peptidomics have catalyzed the identification and quantification of thousands of endogenous peptides across diverse biological systems. However, the vast peptidomic landscape generated by proteolytic processing poses several challenges for downstream analyses and limits the comparability of clinical samples. Here, we present an algorithm that aggregates peptides into peptide clusters, reducing the dimensionality of peptidomics data, improving the definition of protease cut sites, enhancing inter-sample comparability, and enabling the implementation of large-scale data analysis methods akin to those employed in other omics fields. We showcase the algorithm by performing large-scale quantitative analysis of wound fluid peptidomes of highly defined porcine wound infections and human clinical non-healing wounds. This revealed signature phenotype-specific peptide regions and proteolytic activity at the earliest stages of bacterial colonization. We validated the method on the urinary peptidome of type 1 diabetics which revealed potential subgroups and improved classification accuracy.

PDIA iminosugar influence on subcutaneous Staphylococcus aureus and Pseudomonas aeruginosa infections in mice.

Introduction: Biofilm-associated infections persist as a therapeutic challenge in contemporary medicine. The efficacy of antibiotic therapies is ineffective in numerous instances, necessitating a heightened focus on exploring novel anti-biofilm medical strategies. Among these, iminosugars emerge as a distinctive class of compounds displaying promising biofilm inhibition properties. Methods: This study employs an in vivo wound infection mouse model to evaluate the effectiveness of PDIA in treating biofilm-associated skin wound infections caused by Staphylococcus aureus and Pseudomonas aeruginosa. Dermic wounds in mice were infected with biofilm-forming strains, specifically S. aureus 48 and P. aeruginosa 5, which were isolated from patients with diabetic foot, and are well-known for their strong biofilm formation. The subsequent analysis included clinical, microbiological, and histopathological parameters. Furthermore, an exploration into the susceptibility of the infectious strains to hydrogen peroxide was conducted, acknowledging its potential presence during induced inflammation in mouse dermal wounds within an in vivo model. Results: The findings revealed the efficacy of PDIA iminosugar against the S. aureus strain, evidenced by a reduction in bacterial numbers within the wound and the inflammatory focus. Discussion: This study suggests that PDIA iminosugar emerges as an active and potentially effective antibiofilm agent, positioning it as a viable treatment option for staphylococcal infections.

Pediatric wound infections following 2023 Kahramanmaras earthquakes: case series.

BACKGROUND: The Kahramanmaras earthquakes in Turkey on February 6, 2023, resulted in more than 100 000 injuries and 50 500 deaths. The main causes of morbidity and mortality in earthquake-affected patients include crush syndrome, trauma-related extremity injuries, and wound infections. OBJECTIVE: To investigate infective complications, causative microorganisms, treatments, and treatment responses in pediatric patients. METHODS: The case series involved 12 earthquake victims admitted to a tertiary treatment center between February 9 and 24, 2023. Wound sample cultures were obtained from patients with infected wounds via wound secretions and tissue samples collected during surgery. RESULTS: Nine patients were male (75%), and the mean age of patients was 12.6 ± 3.7 years. Seven patients (58.3%) experienced crush syndrome. Seven patients (58.3%) underwent fasciotomy operations. The main infectious complications were wound infections (58.3%) and urinary tract infections (25%). Nine different organisms were found to cause wound infection, with Enterococcus faecium (41.6%), Acinetobacter baumanii (33.3%), and Pseudomonas aeruginosa (16.6%) being the major bacterial isolates. All Acinetobacter strains were multidrug-resistant (MDR). CONCLUSION: Major disasters such as earthquakes are rare, and infections are the major complications that increase morbidity and mortality. Initial appropriate treatment contributes to improved outcomes, as MDR strains are common pathogens in these patients.