Search Results (263)

The emergence and spread of antimicrobial resistance among pathogens are significantly reducing available therapeutic options, highlighting the urgent need for novel and complementary treatment strategies. Antimicrobial photodynamic therapy (aPDT) is a promising alternative approach that can overcome antimicrobial resistance through a multitarget mechanism of action, exerting direct bactericidal and fungicidal effects with minimal risk of resistance development. Although aPDT has shown efficacy against a variety of pathogens, data on its activity against large collections of clinical multidrug-resistant strains are still limited. In this study, we assessed the antimicrobial activity of the photosensitizer RLP068/Cl combined with a red light-emitting LED source at 630 nm (Molteni Farmaceutici, Italy) against a large panel of Gram-negative and Gram-positive bacterial strains harboring relevant resistance traits and Candida species. Our results demonstrated the significant microbicidal activity of RLP068/Cl against all of the tested strains regardless of their resistance phenotype, with particularly prominent activity against Gram-positive bacteria (range of bactericidal concentrations 0.05–0.1 µM), which required significantly lower exposure to photosensitizer compared to Candida and Gram-negative species (range 5–20 µM). Overall, these findings support the potential use of RLP068/Cl-mediated aPDT as an effective therapeutic strategy for the management of localized infections caused by MDR organisms, particularly when conventional therapeutic options are limited. Full article

Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article

Studies on plant extracts as growth promoters and immunostimulants have shown promising results. However, their effects on fish health and growth remain unclear. This study evaluated the in vitro and in vivo effects of Eucalyptus globulus pyroligneous extract (PE) on Nile tilapia. In vitro, minimal inhibitory and bactericidal concentration (MIC and MBC) and antibiogram analyses showed that PE could eliminate key bacterial strains affecting fish and human health, but only if its volatile components were preserved. In vivo, Oreochromis niloticus juveniles were fed diets containing 0.5% and 1% PE. We assessed fish hematology, phagocytosis, survival against Streptococcus agalactiae, and growth parameters. Fish fed 1% PE had lower erythrocyte and lymphocyte counts but higher neutrophil levels than controls. Their phagocytic capacity was significantly enhanced compared to both the control and 0.5% groups. However, the 0.5% PE group had a higher phagocytic index than both the control and 1% groups. No protection against S. agalactiae or significant effects on growth were observed. In conclusion, distilled E. globulus PE shows potential as an immunostimulant for fish. However, further studies are needed to preserve its volatile compounds and optimize its use in aquaculture. Full article

The emergence of multidrug-resistant pathogens has driven the development of novel antimicrobial peptides (AMPs) as therapeutic alternatives. Lactolisterin LBU (LBU) is a bacteriocin with promising activity against Gram-positive bacteria, including Staphylococcus aureus. In this study, we designed and evaluated a panel of amino acid variants of LBU to investigate domain–activity relationships and improve activity. Peptides were commercially synthesized, and their effect was evaluated for minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), hemolytic activity, cytotoxicity, in vivo toxicity, and virulence modulation. AlphaFold3 structural prediction of LBU revealed a four-helix topology with amphipathic and hydrophobic segments. Helical wheel projections identified helices I and IV as amphipathic, suggesting their potential involvement in membrane interaction and activity. Glycine-to-alanine substitutions at helix I markedly increased antimicrobial activity but altered toxicity profiles. In contrast, changes at helix junctions and kinks reduced antimicrobial activity. We also showed differential regulation of virulence genes upon sub-MIC treatment. Overall, rational substitution enabled identification of residues critical for activity and toxicity, providing insights into therapeutic tuning of lactolisterin-based peptides. Full article

Background/Objective: Platelet concentrates (PCs) are used in transfusion medicine to treat bleeding disorders. Staphylococcus aureus, a predominant PC contaminant, has been implicated in several adverse transfusion reactions. The aim of this study was to investigate the impact of PC storage on S. aureus resistance to quinolones, which are commonly used to treat S. aureus infections. Methods/Results: Four transfusion-relevant S. aureus strains (TRSs) were subjected to comparative transcriptome analyses when grown in PCs vs. trypticase soy broth (TSB). Results of these analyses revealed differentially expressed genes involved in antibiotic resistance. Of interest, the norB gene (encodes for the NorB efflux pump, which is implicated in quinolone resistance and is negatively regulated by MgrA) was upregulated (1.2–4.7-fold increase) in all PC-grown TRS compared to TSB cultures. Minimal Bactericidal Concentration (MBC) of ciprofloxacin and norfloxacin in PC-grown TRS compared to TSB showed increased resistance to both quinolones in PC cultures. Complementary studies with non-transfusion-relevant strains S. aureus RN6390 and its norB and mgrA deletion mutants were conducted. MBC of ciprofloxacin and norfloxacin and RT-qPCR assays of these strains showed that not only norB, but also norA and norC may be involved in enhanced quinolone resistance in PC-grown S. aureus. The role of norB in S. aureus virulence was also tested using the silkworm Bombyx mori animal model; lethal dose 50 (LD₅₀) assays revealed slightly higher virulence in larvae infected with the wild-type strain compared to the norB mutant. Conclusions: The PC storage environment enhances quinolone resistance in S. aureus and induces differential expression of efflux pump nor genes. Furthermore, our preliminary data of the involvement of NorB in virulence of S. aureus using a silkworm model merit further investigation with other systems such as a mammal animal model. Our results provide mechanistic insights to aid clinicians in the selection of antimicrobial treatment of patients receiving transfusions of S. aureus-contaminated PCs. Full article

Background: Urinary tract infections (UTIs) caused by the multidrug resistance (MDR) phenotype termed extended-spectrum beta lactamase (ESBL)-producing E. coli is a significant and growing global health concern. In response to the rising prevalence, the novel Beta Lactam-Beta Lactamase inhibitor (BL/BLI) combinations have been introduced in recent years. While these agents have shown efficacy, their clinical utility is constrained by high cost, limited availability, and emerging resistance mechanisms. The rational of this study was to test the in vitro activity of a cost-effective alternative to currently available BL–BLI combinations against ESBL-producing E. coli isolated from urinary tract infections (UTIs). Objective: This study investigates the in vitro antimicrobial activity of cefaclor (CFC), both as monotherapy and in combination with the β-lactamase inhibitors clavulanic acid (CA) and sulbactam (SUL), against 52 ESBL-producing E. coli isolates derived from urine cultures of patients diagnosed with UTIs. Methods: The susceptibility ranges were measured by disk diffusion and minimal inhibitory concentration (MIC) methods. In addition, the Time kill assay and disk approximation method were performed to measure the synergistic and bactericidal activity of the approached combination. Results: The MIC50 and MIC90 for CFC were improved from more than 128 µg/mL to 8/4 µg/mL when CFC was combined with either CA or SUL. The triple combination format of CFC/CA/SUL showed MIC50 and MIC90 values at 8/4/4 µg/mL and 64/32/32 µg/mL, respectively. The recovered susceptibility percentages were 54%, 54%, and 58% for CFC/CA, CFC/SUL, and CFC/CA/SUL combinations, respectively. Disk approximation and time–kill assay results revealed synergy and bactericidal effects when CFC combined with CA or SUL for isolates that showed susceptibility restorations of CFC when coupled with CA or SUL by the disk diffusion and MIC method. Conclusions: This study proposes a cost-effective combination that could mitigate resistance development and offer a sparing option to last resort treatment choices including carbapenems. However, testing efficacy in a clinical setting is crucial. Full article

Plantago ovata has been utilized as an effective natural remedy with minimal side effects, offering a promising alternative to synthetic pharmaceuticals. The supercritical fluid extraction (SFE) of Plantago ovata leaves yielded 0.417 g and 0.532 g at 40 °C and 80 °C, respectively. The 40 °C extract exhibited stronger antimicrobial activity, with minimum inhibitory concentrations (MICs) as low as 15.62 µg/mL and minimum bactericidal concentrations (MBCs) as low as 31.25 µg/mL against Bacillus subtilis and Candida albicans. In contrast, the 80 °C extract demonstrated reduced activity, with MICs and MBCs up to 250 and 500 µg/mL, respectively. The 40 °C extract also showed superior lipase inhibition (IC₅₀ = 17.21 µg/mL) compared to the 80 °C extract (IC₅₀ = 26.42 µg/mL), although orlistat remained the most potent (IC₅₀ = 6.02 µg/mL). In addition, cytotoxicity assays revealed stronger effects of the 40 °C extract on Caco-2 colon cancer cells (IC₅₀ = 109.47 µg/mL) compared to the 80 °C extract (IC₅₀ = 174.81 µg/mL). These results suggest that the lower-temperature SFE of P. ovata yields extracts with enhanced antimicrobial, anti-obesity, and anticancer activities, supporting its potential for pharmaceutical and nutraceutical applications. Full article

Background/Objectives: Biocorrosion, driven by microbial colonization and biofilm formation, poses a significant threat to the integrity of metal artifacts, particularly those composed of copper and its alloys. Pseudomonas aeruginosa, a bacterial species that reduces nitrates, plays a key role in this process. This study explores the potential of two metabolite-rich plant extracts, Aloe vera and Opuntia ficus-indica, as sustainable biobased inhibitors of microbial-induced corrosion (MICOR). Methods: The antibacterial and antibiofilm activities of the extracts were evaluated using minimal inhibitory concentration (MIC) assays, time-kill kinetics, and biofilm prevention and removal tests on copper, bronze, and brass samples. Spectrophotometric and microbiological methods were used to quantify bacterial growth and biofilm density. Results: Both extracts exhibited significant antibacterial activity, with MIC values of 8.3% (v/v). A. vera demonstrated superior bactericidal effects, achieving reductions of ≥3 log₁₀ in bacterial counts at lower concentrations. In antibiofilm assays, both extracts effectively prevented biofilm formation and reduced established biofilms, with A. vera exhibiting greater efficacy against them. The active metabolites—anthraquinones, phenolics, flavonoids, and tannins—likely contribute to these effects. Conclusions: These findings highlight the dual role of A. vera and O. ficus-indica extracts as both corrosion and biocorrosion inhibitors. The secondary metabolite profiles of these plants support their application as eco-friendly alternatives in the conservation of metal cultural heritage objects. Full article

Background: Endophthalmitis, associated with intraocular procedures, is an infection of the eye that can rapidly result in substantial irreversible loss of vision and may even lead to removal of the eye. Prevention strategies vary globally and often include antibiotic use—often consisting of a broad-spectrum mono-therapeutic agent. The purpose of this study is to test the efficacy and value of combinations of cefuroxime (cefu), cefazolin (cefa), azithromycin (azith), and/or tobramycin (tob) as alternatives to the use of moxifloxacin. We looked for synergism since these antimicrobials used different mechanisms of inhibition. Methods: Initially, we examined individual antimicrobials to determine the minimal bactericidal concentrations (MBC) of each individual treatment against Klebsiella pneumonia, Pseudomonas aeruginosa, Staphylococcus aureus, two clinical isolates of MRSA, and Staphylococcus epidermidis, by both the Zone of Inhibition (ZOI) and the Colony Forming Unit (CFU) assays. We then used these data in a combinatorial study. Results: We found combinations that were synergistic against all the bacteria tested, resulting in total eradication [8 logs] of all bacteria. We found that the ZOI assay provided less consistent results than the CFU assays. Conclusions: We have found combinations of these antimicrobials that were synergistic in the total eradication (8 logs) of all bacteria tested. These three combinations were: cefuroxime/azithromycin; azithromycin/tobramycin; and cefuroxime/tobramycin. Moxifloxacin (Vigamox) did not completely eradicate Staphylococcus epidermidis. These combinations can then be used as eye drops to serve as a prophylactic for endophthalmitis after eye injections and eye surgery. Full article

Polymeric antibacterial agents are attracting attention due to their increased bactericidal efficiency and low probability of causing drug resistance. Their activity, usually attributed to electrostatic interactions and subsequent disruption of cell membranes, is attributed to the number and chemical structure of their functional groups. In this study, hyperbranched polyethyleneimines (PEIs) of two different molecular weights were functionalized with amphiphilic alkyltriphenylphosphonium groups, which are known to induce membrane penetration, especially in cells with high membrane potential. The obtained nanoparticles were chemically and physicochemically characterized, and their inhibition potential against Gram (−) E. coli and Gram (+) S. aureus bacteria was determined. The effects of polymer molecular weight, alkyl chain length, and the number of triphenylphosphonium groups on their antimicrobial efficacy were studied. All compounds exhibited antibacterial properties, especially against S. aureus (MIC < 50 μg/mL). Low-molecular-weight polymeric derivatives and longer alkyl chains proved more efficient against both E. coli (MIC = 20 μg/mL) and S. aureus (MIC = 0.25 μg/mL). SEM images depicted changes in cell morphology, bacterial membrane disruption, and leakage of intracellular contents, signifying loss of cell viability. Minimal cytotoxicity against three mammalian cell lines at relevant antibacterial concentrations demonstrated the potential of a structure–property relationship approach for novel potent antibacterial polymers. Full article

Extensive use of classical antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. To combat this challenge, researchers have turned to the antimicrobial peptides (AMPs). Aurein 1.2 (GLFDIIKKIAESF-NH2) was demonstrated to have broad spectrum bi-functionality against bacterial and cancer cells. The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of new analogs of aurein 1.2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. The antibacterial activity was estimated against Gram-positive and Gram-negative bacteria using broth microdilution method in concentrations from 0 to 320 µg/mL to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The antiproliferative activity test shows that the peptide analog EH [Orn]⁸ has the highest activity (IC₅₀ = 44 ± 38 μM) for the three cell lines studied (MCF-12F, MCF-7, and MDA-MB-231). The same compound exhibited good antimicrobial activity. The obtained results reveal that replacement of Lys with non-proteinogenic amino acids can increase both the potency and activity spectra of natural template peptides, making them suitable candidates for new drug development. Full article

Minimally processed foods (MPFs), often considered ready-to-eat, do not undergo cooking and therefore require proper handling and preparation to ensure safety. If not handled correctly, these foods can serve as a pathway for diseases caused by pathogenic bacteria, including Escherichia coli and Salmonella spp. The antibacterial activity of essential oils (EOs) has been increasingly studied as a tool for controlling microorganisms in the food sector. Therefore, we aimed to verify the contamination of MPF by E. coli and Salmonella and to test the sensitivity of these strains to Copaifera langsdorffii, Schinus terebinthifolius, Citrus reticulata, Eucalyptus citriodora, Elettaria cardamomum, Ocimum basilicum, and Eugenia caryophyllus EOs using the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. From 25 MPF samples, one E. coli strain and one Salmonella spp. were isolated. C. langsdorffii and C. reticulata EOs did not show antibacterial activity, while S. terebinthifolius and E. citriodora inhibited the growth of both strains. The E. cardamomum, O. basilicum, and E. caryophyllus EOs presented inhibitory and bactericidal responses at concentrations 0.78, 0.39, and 0.19% (v/v), respectively, compared to the two isolated strains. The present study reinforces the antibacterial potential of EOs and suggests their application in the MPF production chain. Full article

Background/Objectives: Biofilm-embedded bacteria, such as Pseudomonas aeruginosa (P. aeruginosa), are highly resistant to antibiotics, making their treatment challenging. Plant-based natural compounds (PBCs) and metal(loid)-based antimicrobials (MBAs) are promising alternatives. This study evaluated the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and synergistic effects of zinc sulfate (ZnSO₄), carvacrol (CV), and antibiotics (ciprofloxacin [CIP], tobramycin [TOB], and azithromycin [AZM]) against P. aeruginosa PAO1. Methods: The MIC and MBC of ZnSO₄, CV, and antibiotics were determined using a 96-well plate method. Cytotoxicity was assessed via MTT assay. Fractional inhibitory concentration (FIC), fractional bactericidal concentration (FBC), minimal biofilm inhibition concentration (MBIC), and minimum biofilm eradication concentration (MBEC) indices were calculated for each combination of agents. Checkerboard assays identified interactions, and the effectiveness of combinations was further evaluated in a mouse chronic lung infection model with treatments delivered intratracheally, intraperitoneally, and orally. Results: TOB had the lowest MIC and MBC values, proving most effective against P. aeruginosa PAO1. Strong synergy was observed with CV + ZnSO₄ (CV + Zn) combined with CIP, CV with CIP, and CV + Zn with TOB, as indicated by low FIC indices. CV + Zn with TOB and CV with TOB had low FBC indices, while CV + Zn with AZM showed antagonism. In vivo, intratracheal TOB + CV + Zn reduced lung inflammation and tissue involvement, yielding the best histopathological outcomes. The MIC of CIP and TOB was reduced 5-fold and 4-fold, respectively, when combined with CV + Zn. Conclusions: CV + Zn demonstrated strong synergistic effects with antibiotics and effectively managed P. aeruginosa lung infections in mice. These findings highlight its potential as an innovative therapy for biofilm-associated infections. Full article

Copper (II) oxide nanoparticles (CuO NPs) attract much attention as a promising antimicrobial agent. We studied the antibacterial properties of three types of CuO NPs against Escherichia coli bacteria: flake-shaped particles with a diameter of 50–200 nm and a thickness of 10–20 nm (CuO-CD synthesized by chemical deposition), spherical particles with a size of 20–90 nm (CuO-EE obtained by electrical explosion), and rod-shaped particles with a length of 100–200 nm and a diameter of 30 × 70 nm (CuO-CS commercial sample). We tested how the shape, size, and concentration of the NPs, and composition of the dispersion medium affected the properties of the CuO NPs. We prepared dispersions based on distilled water, a 0.9% NaCl solution, and the LB broth by Lennox and used Triton X-100 and sodium dodecyl sulfate (SDS) as stabilizers. The concentration of NPs was 1–100 mg L⁻¹. We showed that the dispersion medium composition and stabilizer type had the greatest influence on the antibacterial effects of CuO NPs. We observed the maximum antibacterial effect for all CuO NP types dispersed in water without a stabilizer, as well as in LB broth with the SDS stabilizer. The maximum inhibition of culture growth was observed under the influence of CuO-EE (by 30%) and in the LB broth with the SDS stabilizer (by 1.3–1.8 times depending on the type of particles). In the saline solution, the antibacterial effects were minimal; in some cases, the CuO NPs even promoted bacterial culture growth. SDS increased the antibacterial effects of NPs in broth and saline but decreased them in water. Finally, among the particle types, CuO-CS turned out to be the most bactericidal, which is probably due to their rod-shaped morphology and small diameter. At the same time, the concentration and aggregation effects of CuO NPs in the colloidal systems we studied did not have a linear action on their antibacterial properties. These results can be used in the development of antibacterial coatings and preparations based on CuO NPs to achieve their maximum efficiency, taking into account the expected conditions of their use. Full article

Background and Objectives: This study introduces an innovative approach to accelerating wound healing by leveraging the bactericidal properties of mycosynthesized copper oxide nanoparticles (CuO-NPs) and their combination with curcumin against Pseudomonas aeruginosa. The study aims to evaluate their antimicrobial efficacy, impact on quorum sensing-associated virulence factors, and potential therapeutic applications in wound healing. Materials and Methods: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CuO-NPs were determined to be 25 μg/mL and 50 μg/mL, respectively. At sub-inhibitory concentrations (0.5 MIC, 0.25 MIC, and 0.125 MIC), their effects on P. aeruginosa growth and quorum sensing-associated virulence factors were assessed. Antioxidant activity and cytotoxicity were also evaluated. Additionally, the combination of CuO-NPs and curcumin (CUR) was tested for its enhanced wound-healing efficacy. Results: While CuO-NPs did not inhibit P. aeruginosa growth at sub-inhibitory concentrations, they significantly reduced quorum sensing-associated virulence factors in a dose-dependent manner: LasB elastase (81.8%, 60.6%, and 53.03%), LasA protease (70%, 68.5%, and 57.1%), and pyocyanin (85.7%, 71.4%, and 55.9%). CuO-NPs exhibited strong antioxidant activity by scavenging free radicals. The combination of CuO-NPs and CUR demonstrated the highest wound-healing efficacy, outperforming the negative control and Mebo ointment by 193.9% and 61.6%, respectively. Additionally, CuO-NPs exhibited selective cytotoxicity against HepG2 cancer cells while displaying minimal toxicity toward normal human skin cells. Conclusions: CuO-NPs, particularly in combination with CUR, show promising potential as a therapeutic agent for wound healing by inhibiting quorum sensing-associated virulence factors, exhibiting strong antioxidant activity, and demonstrating selective cytotoxicity. These findings highlight their potential biomedical applications. Full article