Search Results (185)

This study presents a novel hydrogel formulation combining mupirocin, a broad-spectrum antibiotic, with keratinocyte growth factor (KGF) to enhance wound healing through antibacterial action and tissue regeneration. Mupirocin was encapsulated in hydroxypropyl β-cyclodextrin (HP-β-CD) and stabilized with poly(amidoamine) dendrimers (PAMAM). Molecular docking studies assessed mupirocin’s binding to PAMAM and its interaction with isoleucyl-tRNA synthetase. Physicochemical properties—including zeta potential, particle size, and surface tension—were characterized, and drug release kinetics were evaluated using Franz diffusion cells. In vitro assays on human dermal fibroblasts (HS27) included proliferation, scratch wound healing, and flow cytometry to assess cellular behavior. Antibacterial efficacy was determined via the Kirby–Bauer disk diffusion method. Results showed strong binding of mupirocin to its target enzyme, enhanced by KGF. The hydrogel exhibited favorable properties: surface tension of 24.7 dyne/cm, zeta potential of −24.79 mV, and particle size of ~119 nm, indicating high stability. Franz diffusion revealed sustained drug release compared to commercial mupirocin. Cellular assays demonstrated significant fibroblast migration and proliferation, with flow cytometry confirming increased wound healing markers. The formulation showed potent antimicrobial activity, including against Methicillin-resistant Staphylococcus aureus (MRSA), highlighting its promise for infected wound treatment and advanced clinical wound care. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major cause of bloodstream infection worldwide. In Korea, sequence type (ST) 72 has predominated, whereas ST8, including the USA300 lineage, has recently emerged. Comparative data on these genotypes in MRSA bacteremia (MRSAB) are limited. We conducted a retrospective cohort study of adult patients with MRSAB admitted to a 2700-bed tertiary care hospital in Republic of Korea between July 2008 and December 2020. Clinical features and outcomes of patients with ST8 MRSA were compared with those of patients with ST72 MRSA. Among 1975 cases of S. aureus bacteremia, 998 (50.5%) were due to MRSA, including 327 (32.7%) ST72 and 23 (2.3%) ST8 isolates. Demographics and comorbidities were similar, though pneumonia appeared more frequent in ST8 cases without statistical significance. ST8 isolates exhibited greater resistance to ciprofloxacin and erythromycin and more frequent vancomycin E-test MICs ≥1 mg/L, while broth microdilution MICs were comparable. spa type distribution differed, with t324 predominating in ST72 and t008 in ST8. Management practices, persistent bacteremia, recurrence, and 30- and 90-day mortality did not differ significantly. In multivariable analysis, liver cirrhosis and Charlson comorbidity index >4, but not MRSA genotype, independently predicted 30-day mortality. These findings highlight the importance of continued surveillance of emerging ST8 clones. Full article

This study presents the development of an advanced three-dimensional (3D) bioprinted skin scaffold integrating sodium alginate (SA), gelatin (Gel), human skin-derived decellularized extracellular matrix (dECM), and microbiota-derived postbiotics. To ensure a biocompatible and functional ECM source, human skin samples collected during elective aesthetic surgical procedures were utilized. Following enzymatic treatment, the dermal layer was carefully separated from the epidermis and subjected to four different decellularization protocols. Among them, Protocol IV emerged as the most suitable, achieving significant DNA removal while maintaining the structural and biochemical integrity of the ECM, as confirmed by Fourier-transform infrared spectroscopy. Building on this optimized dECM-4, microbiota-derived postbiotics from Limosilactobacillus reuteri EIR/Spx-2 were incorporated to further enhance the scaffold’s bioactivity. Hybrid scaffolds were then fabricated using 7% Gel, 2% SA, 1% dECM-4, and 40 mg/mL postbiotics in five-layered grid structures via 3D bioprinting technology. Although this composition resulted in reduced mechanical strength, it exhibited improved hydrophilicity and biodegradability. Moreover, antimicrobial assays demonstrated inhibition zones of 16 mm and 13 mm against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) and Pseudomonas aeruginosa (ATCC 27853), respectively. Importantly, biocompatibility was confirmed through in vitro studies using human keratinocyte (HaCaT) cells, which adhered, proliferated, and maintained normal morphology over a 7-day culture period. Taken together, these findings suggest that the engineered hybrid scaffold provides both regenerative support and antimicrobial protection, making it a strong candidate for clinical applications, particularly in the management of chronic wounds. Full article

This study explores the development of biocompatible hydrogel dressings incorporating curcumin as an alternative antibacterial agent. In this context, hydrogels were prepared using polyvinyl alcohol, xanthan gum, gelatin, and curcumin as a therapeutic component. FTIR spectroscopy confirmed the successful incorporation of curcumin into the hydrogel matrix, while release profiles demonstrated sustained release. Mechanical testing indicated that xanthan gum reduced elongation and strength in hydrogels, while the combination of xanthan gum and gelatin increased stiffness without loss of elasticity. Curcumin had no major effect on the tensile and rheological properties, preserving the structural integrity of the hydrogels. The hydrogels demonstrated antibacterial activity against Pseudomonas aeruginosa and Staphylococcus aureus ATCC strains, as well as multidrug methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. Biocompatibility was confirmed through viability assays with immortalized human keratinocytes (HaCaT) and adult human dermal fibroblasts (HDFa), showing no acute cytotoxic effects after 48 h of exposure. Their effective action against clinically relevant bacteria and high cytocompatibility position these hydrogels as promising candidates for infection management and antibiotic resistance mitigation in wound care applications. Full article

Staphylococcus aureus colonizes the nasal and pharyngeal mucosa of a considerable proportion of the human population, representing a relevant reservoir for the dissemination of antibiotic resistance. This study aimed to determine the prevalence, antibiotic resistance profiles, and molecular characterization of S. aureus strains isolated from the nose and pharynx of healthy individuals of Mexico City, Mexico. Nasal and pharyngeal swabs were taken from 1777 individuals aged between 1 and 99 years. Microbiological identification, antibiotic susceptibility testing, virulence gene detection, SCCmec typing, and spa-typing allowed the characterization of 1459 strains. S. aureus colonization was found in 59.7% of the population, with more of these strains being found in the pharynx than in the nose. MRSA constituted 9.25% of the strains, with a predominance of strains with SCCmec types IV and IVa. The most frequent resistance of S. aureus strains was to penicillin (87.6%), clindamycin (43.4%) and erythromycin (27.2%), with no statistical differences regarding the anatomical sites of isolation. The most frequently found virulence genes were lukE-D, icaA, sdrC, coa, and gyrA. Sixty-two spa-types were identified, and t-189 was the most common. These findings reflect a high colonization rate and genetic diversity, highlighting the importance of considering both anatomical sites in S. aureus surveillance studies. Full article

Chronic wounds pose a great challenge due to their slow healing and susceptibility to infections, hence the need for innovative alternatives to conventional antibiotics, as increasing bacterial resistance limits the efficacy of current treatments. This paper addresses the development of novel electrospun membranes based on polyvinyl alcohol (PVA) and sodium alginate, incorporating therapeutic ZnO and bioglass (54SiO₂:40CaO:6P₂O₅) nanoparticles. While nanocomposites presented smaller fiber diameters than pure polymers, ternary nanocomposites displayed higher values, e.g., in porous areas, values were in the ca. 80–240 nm range and 0.06–0.60 μm², respectively. The Young’s modulus of the PVA/SA membrane, initially 15.9 ± 2.0 MPa, decreased by 65% with 10 wt.% ZnO NPs, whereas 10 wt.% BG NPs increased it by 100%. The membranes demonstrated efficacy against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) isolated from a human wound secretion, as well as two ATCC strains: Staphylococcus aureus and Staphylococcus epidermidis. A cell viability assay conducted with HaCaT cells demonstrated nearly complete survival following 72 h of membrane exposure. Their combined Gram-positive antibacterial activity and cytocompatibility support their potential application as biofunctional dressings for the management of chronic and hospital-acquired topical infections, while also contributing to the global effort to combat antibiotic resistance. Full article

This study explores the potential of biodegradable Bioglass 45S5 formulations as a dual-function approach for preventing and treating Staphylococcus aureus infections in orthopaedic surgery while addressing the growing concern of antimicrobial resistance (AMR). The research focuses on the development and characterisation of antibiotic-loaded BG45S5 formulations, assessing parameters such as drug loading efficiency, release kinetics, antimicrobial efficacy, and dissolution behaviour. Key findings indicate that the F2l-BG45S5-T-T-1.5 and F2l-BG45S5-T-V-1.5 formulations demonstrated controlled antibiotic release for up to seven days, with size distributions of D(10): 7.11 ± 0.806 µm, 4.96 ± 0.007 µm; D(50): 25.34 ± 1.730 µm, 25.20.7 ± 0.425 µm; and D(90): 53.7 ± 7.95 µm, 56.10 ± 0.579 µm, respectively. These formulations facilitated hydroxyapatite formation on their surfaces, indicative of osteogenic potential. The antimicrobial assessments revealed zones of inhibition against methicillin-susceptible Staphylococcus aureus (MSSA, ATCC-6538) measuring 20.3 ± 1.44 mm and 24.6 ± 1.32 mm, while for methicillin-resistant Staphylococcus aureus (MRSA, ATCC-43300), the inhibition zones were 21.6 ± 1.89 mm and 22 ± 0.28 mm, respectively. Time-kill assay results showed complete bacterial eradication within eight hours. Additionally, biocompatibility testing via MTT assay confirmed cell viability of >75%. In conclusion, these findings highlight the promise of antibiotic-loaded BG45S5 as a multifunctional biomaterial capable of both combating bone infections and supporting bone regeneration. These promising results suggest that in vivo studies should be undertaken to expedite these materials into clinical applications. Full article

Secondary methicillin-resistant Staphylococcus aureus (MRSA) infection causes high mortality in patients with influenza A virus (IAV). Our previous study observed that the relative abundance of Lactobacillus murinus (L. murinus) was significantly reduced in both the respiratory tract and gut of IAV-infected mice and negatively correlated with the severity of IAV–MRSA coinfection pneumonia, but the role of L. murinus remains unclear. Here, we supplemented the respiratory tract and gut of IAV-infected mice with live L. murinus and performed a secondary MRSA infection challenge to investigate the effects and potential mechanisms further. Data showed that L. murinus supplementation significantly reduced mortality and pathogen loads in IAV–MRSA coinfected mice and upregulated the lung T cell-independent (TI) IgA response in IAV-infected mice. The 16S rRNA gene sequencing results showed that L. murinus supplementation ameliorated microbiota composition disorder and regulated metabolic dysfunction in the gut of IAV-infected mice. The correlation analysis and antibiotic cocktail treatment experiment showed that the TI IgA response in lungs is dependent on gut microbiota. These findings demonstrated that L. murinus supplementation reduces susceptibility to secondary MRSA infection in IAV-infected mice by promoting the TI IgA response, and provide a new perspective on the use of probiotics to prevent secondary bacterial infection following IAV infection. Full article

This study elucidates potential genetic determinants and mechanisms involved in the synergistic effects of daptomycin (DAP) + fosfomycin (FOF) combination therapy. Among 33 clinically derived DAP-susceptible (S)/DAP-resistant (R) isogenic strain pairs, mutations in the mprF gene occurred in 30/33 DAP-R strains, including polymorphisms of L826F (33%) or T345A/L/I (15%). Strain variants of DAP-S CB1483 serially passaged in vitro for 10 days in DAP +/− FOF identified a key non-synonymous mutation in mprF (L826F) only in the DAP monotherapy arm. Interestingly, passage in FOF alone or DAP + FOF prevented the emergence of this mprF mutation following 10-day passage. This L826F mprF polymorphism, associated with a “gain-in-function” phenotype, exhibited increased amounts of lysyl-phosphatidylglycerol (L-PG) in the cell membrane (CM). Transcriptomics revealed a relatively modest number (~10) of distinct genes that were significantly up- or downregulated (≥2 log fold) in both the DAP-S and DAP-R strain pairs upon DAP + FOF exposures (vs. DAP or FOF alone). Of note, DAP + FOF decreased expression of lrgAB and sdrE and increased the expression level of fosB. In a rabbit infective endocarditis (IE) model, the DAP-R CB185 strain treated with DAP +/− FOF showed significantly reduced lrgB expression in vegetations compared with DAP treatment alone. Overall, these findings indicate that DAP + FOF therapy impacts MRSA through multiple specific mechanisms, enhancing bacterial clearance. Full article

Staphylococcus aureus (S. aureus) is a major pathogen responsible for mastitis in dairy cows and can contaminate raw milk, thereby posing significant health risks to consumers. The emergence of methicillin-resistant S. aureus (MRSA) has further heightened public health concerns due to its antibiotic resistance and infectious potential. In this study, we examined the prevalence, virulence genes, antimicrobial resistance, spa types, and biofilm formation of S. aureus isolates from dairy farms in Guangxi Province, China. Among 242 randomly selected samples, 37 S. aureus strains were identified (15.3% infection rate), including 67.5% MRSA. Antibiotic resistance was observed in 78.4% of isolates, with 35.1% exhibiting multidrug resistance (MDR). Enterotoxin gene analysis showed sea as the most common (67.6%), followed by ser (54.1%) and seh (51.4%), whereas seb and selj were absent. All isolates formed biofilms in vitro, with 64.8% showing strong biofilm-forming ability. Staphylococcal protein A (spa) typing classified the 37 S. aureus strains into 11 spa types, with t030 being the most prevalent (43.2%). These findings indicate that S. aureus is moderately prevalent in raw milk, often carrying multiple virulence genes, forming robust biofilms, and showing antimicrobial resistance. The MRSA that is “latent” in raw milk reminds us of the need for monitoring at the farm level. Full article

The objectives of this study were to design, synthesize, and evaluate the antibacterial activity of a series of novel aminoguanidine-tetralone derivatives. Thirty-four new compounds were effectively synthesized through nucleophilic substitution reaction and guanidinylation reaction. Chemical structures of all the desired compounds were identified by NMR and HR-MS spectroscopy. Most of the synthesized compounds showed significant antibacterial activity against ESKAPE pathogens and clinically resistant Staphylococcus aureus (S. aureus) isolates. S. aureus is an important pathogen that has the capacity to cause a variety of diseases, including skin infections, pneumonia, and sepsis. The most active compound, 2D, showed rapid bactericidal activity against S. aureus ATCC 29213 and MRSA-2 with MIC/MBC values of 0.5/4 µg/mL and 1/4 µg/mL, respectively. The hemolytic activity and cytotoxicity of 2D was low, with HC₅₀ and IC_{50(HEK 293-T)} values of 50.65 µg/mL and 13.09 µg/mL, respectively. Compound 2D induced the depolarization of the bacterial membrane and disrupted bacterial membrane integrity, ultimately leading to death. Molecular docking revealed that dihydrofolate reductase (DHFR) may be a potential target for 2D. In the mouse skin abscess model caused by MRSA-2, 2D reduced the abscess volume, decreased bacterial load, and alleviated tissue pathological damage at doses of 5 and 10 mg/kg. Therefore, compound 2D may be a promising drug candidate for antibacterial purposes against S. aureus. Full article

Background: The opportunistic pathogen Staphylococcus aureus causes skin and soft tissue infections that are associated with biofilm formation, and in immunocompromised patients can progress to surgical site infections, pneumonia, bacteremia, sepsis, and even death. Most antibiotics actively damage living, dividing cells on the surface of the biofilm, where there is a high concentration of nutrients and oxygen, while in the depths, where these factors are scarce, slowly growing cells remain. Objectives: The aim of our study was to evaluate the antibiofilm potential of ethyl acetate roots (EtOAcR) and aerial parts (EtOAcAP) extracts from the perennial Bulgarian plant Geum urbanum L. against methicillin-resistant S. aureus (MRSA) NBIMCC 8327. Methods: The effects of both extracts on the expression of biofilm-related genes, icaA and icaD, were investigated. The cytotoxicity of EtOAcR and EtOAcAP on A-375 (human melanoma), A-431 (epidermoid skin cancer) and HaCaT (normal keratinocytes) cell lines, and the induction of apoptosis were determined. Finally, the in vivo skin irritation potential of the most active extract was studied. Results: Both tested extracts inhibited biofilm formation at concentrations that did not affect bacterial growth. Interestingly, the expression of icaA and icaD was upregulated, although the biofilm development was inhibited 72.4–90.5% by EtOAcAP and 18.9–20.4% by EtOAcR at sub-MICs. EtOAcAP extract showed a more favorable cytotoxic profile on non-tumorigenic cells and stronger antineoplastic activity (IC₅₀ = 6.7–14.68 µg/mL) as compared to EtOAcR extract (IC₅₀ = 8.73–23.67 µg/mL). Therefore, a skin irritation test was performed with the EtOAcAP extract at ten-times higher concentrations than the minimum inhibitory one, and, resultantly, the primary irritation index was equal to zero (no skin irritation observed). Conclusions: The EtOAcAP extract was proven to be an effective antistaphylococcal agent with favorable skin tolerance. The extract showed strong antineoplastic activity and antibiofilm effect at sub-MICs, which outlines new prospects for its development as a natural product for specific skin applications in medical practice. Full article

Given the limited genetic characterization of methicillin-resistant Staphylococcus aureus (MRSA) in South Korea, we performed whole-genome sequencing (WGS) on eight MRSA strains isolated from raw fish products, including 327 sliced raw flatfish, 111 flatfish stew products, 85 sliced raw rockfish, and 11 rockfish stew products. Phylogenetic analysis revealed two distinct clusters—comprising five ST72-t324-SCCmecIVc strains and two novel sequence types—as well as a singleton strain (ST630-t4549-SCCmecV). A total of five antimicrobial resistance genes (ARGs), four plasmid replicon genes, three mobile genetic element genes, and seventy-three virulence factor genes were identified, with distinct genetic profiles observed between the clusters. Notably, several MRSA strains were isolated from samples obtained at the same retail market, indicating potential local clustering. Four ST72-t324-SCCmecIVc strains, collected from the same market, shared identical profiles in terms of four ARGs, two plasmid replicons, two mobile genetic elements, and several virulence factor genes. These findings provide valuable insights into the genomic characteristics of MRSA in raw fish products and highlight the need for ongoing surveillance and monitoring efforts in South Korea. Full article

Staphylococcus aureus is a significant bacterial pathogen responsible for a wide range of diseases in both humans and animals. This study aimed to investigate nucleotide sequence variations, gene expression patterns, and serum biomarkers, including acute phase proteins (APPs), hormonal fluctuations, and iron profile parameters in sheep affected by pneumonia. Additionally, the study focused on the isolation and characterization of S. aureus from pneumonic sheep, with particular emphasis on the prevalence of methicillin-resistant S. aureus (MRSA) strains. Blood samples were collected from both healthy and pneumonic sheep for gene expression and biochemical analyses, while nasal swabs from pneumonic sheep were used for bacterial isolation and identification. Out of 100 nasal swabs analyzed, 44% tested positive for Staphylococcus spp., and 61.4% of these were confirmed as S. aureus by PCR. The mecA gene, a key marker of methicillin resistance, was identified in 17 isolates (38.6% of the S. aureus-positive samples). MRSA isolates showed complete resistance to amoxicillin, cloxacillin, and erythromycin, and high resistance to penicillin, amoxicillin, and tetracycline; however, all MRSA strains remained fully susceptible to vancomycin. Gene expression analysis revealed that TLR2, CLEC4E, PTX3, CXCL8, and IL15RA were significantly upregulated (p < 0.05) in pneumonic ewes, while SOCS3 expression was markedly downregulated. Sequence analysis of immune-related genes revealed notable nucleotide differences between healthy and affected animals. Furthermore, the pneumonic group exhibited significantly elevated levels of APPs, cortisol, and growth hormone, along with reduced levels of insulin, T3, and T4. These findings underscore the zoonotic risk posed by MRSA and emphasize the need for robust surveillance and antibiotic stewardship to control its spread. The study also highlights the importance of molecular diagnostics in accurately identifying MRSA and elucidating resistance mechanisms, thereby facilitating targeted treatment and informed management strategies. Full article

Bacterial infections, particularly those caused by multidrug-resistant strains, remain a significant global public health challenge. The growing resistance to traditional antibiotics highlights the urgent need for novel antibacterial strategies. Herein, we successfully synthesized three types of nitrogen-doped carbon dots (tBuCz-CDs, HAH-CDs, and EC-CDs) via hydrothermal method using tert-butyl carbazate, hydroxyacetic acid hydrazide, and ethyl carbazate as precursors. tBuCz-CDs, HAH-CDs, and EC-CDs exhibited potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with minimum inhibitory concentrations (MICs) of 100, 100, and 150 µg/mL, respectively. Their antibacterial effect on MRSA was comparable to that of the widely used antibiotic vancomycin hydrochloride, as shown by the zone of inhibition assay. Furthermore, the carbon dots exhibited low cytotoxicity and hemolytic activity showing their excellent biocompatibility both in vitro and in vivo. They also significantly promoted wound healing compared to untreated controls. Notably, the serial passaging of MRSA exposed to these carbon dots did not result in the bacterial resistance. Mechanistic studies revealed that the carbon dots exerted antibacterial effects through multiple mechanisms, including the disruption of bacterial membranes, inhibition and eradication of biofilm formation, generation of reactive oxygen species, and DNA damage. This work highlights the potential of nitrogen-doped CDs as a promising material for combating drug-resistant bacterial infections and underscores their potential for further biomedical development. Full article