Search Results (339)

Combining antibiotics with propolis is an effective method to combat bacterial drug resistance. Nanoparticles are of interest in the antimicrobial field because of their higher drug stability, solubility, penetration power, and treatment efficacy. In this study, propolis nanoparticles (PNPs) were synthesized, and their antibacterial and anti-biofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) in combination with ampicillin sodium (AS) were analyzed. The PNPs had an average particle diameter of 118.0 nm, a polydispersity index of 0.129, and a zeta potential of −28.2 mV. The fractional inhibitory concentration indices of PNPs and AS against tested MRSA strains highlighted this synergy, ranging between 0.375 and 0.5. Crystal violet staining showed that combined PNPs and AS significantly inhibited biofilm formation and reduced existing biofilm biomass. We then discovered that PNPs inhibited bacterial adhesion, extracellular polysaccharide synthesis, and mecR1, mecA, blaZ, and icaADBC gene expression. These results indicated that PNPs exerted a synergistic antibacterial effect with AS by inhibiting mecR1, mecA, and blaZ gene expressions to reduce the drug resistance of MRSA. Meanwhile, PNPs weakened bacterial adhesion and aggregation by suppressing icaADBC gene expression, allowing antibiotics to penetrate the biofilm, and exhibiting significant synergistic anti-biofilm activity. In summary, PNPs are promising candidates for combating MRSA-related diseases. Full article

Candida fungal species are the most common fungal opportunistic pathogens. Their ability to form antifungal resistant biofilms contributes to their increasing clinical frequency. These fungi express surface-anchored adhesins including members of the Als family. These adhesins mediate epithelial adhesion, aggregation, and biofilm formation. Many of the adhesins contain cross-β core sequences that form amyloid-like protein aggregates on the fungal surface. The aggregates mediate high-avidity bonding that contributes to biofilm establishment and persistence. Accordingly, autopsy sections from individuals with candidiasis and other mycoses have amyloids within abscesses. An amyloid-forming peptide containing a sequence from Candida albicans Als5 bound to C. albicans, C. tropicalis, and C. parapsilosis. C. albicans and C. tropicalis aggregated with beads coated with serum albumin, and the aggregates stained with the amyloid-binding dye thioflavin T. Additionally, an Als5-derived amyloid-inhibiting peptide blocked cell aggregation. The amyloid-inhibiting peptide also blocked C. albicans, C. tropicalis, and C. parapsilosis adhesion to monolayers of FaDu epithelial cells. These results show the involvement of amyloid-like interactions in pathogenesis in several Candida species. Full article

The war between humans and bacteria started centuries ago. With the advent of antibiotics, there was a temporary ceasefire in this war, but the scenario soon started becoming worse with the emergence of drug-resistant strains within years of the deployment of antibiotics in the market. With the surge in the misuse of antibiotics, there was a drastic increase in the number of multidrug-resistant (MDR) and extensively drug-resistant bacterial strains, even to antibiotics like Methicillin and vancomycin, aggravating the healthcare scenario. The threat of MDR ESKAPE pathogens is particularly high in nosocomial infections, where biofilms formed by bacteria create a protective barrier that makes them highly resistant to antibiotics, complicating the treatment efforts. Scientists are looking at natural and sustainable solutions, as several studies have projected deaths contributed by drug-resistant bacteria to go beyond 50 million by 2050. Many plant-derived metabolites have shown excellent antibacterial and antibiofilm properties that can be tapped for combating superbugs. The present review explores the current status of various studies on antibacterial plant metabolites like alkaloids and flavonoids and their mechanisms in disrupting biofilms and killing bacteria by way of inhibiting key survival strategies of bacteria like motility, quorum-sensing, reactive oxygen species production, and adhesion. These mechanisms were found to be varied in Gram-positive, Gram-negative, and acid-fast bacteria like Mycobacterium tuberculosis, which will be discussed in detail. The successful tapping of the benefits of such plant-derived chemicals in combination with evolving techniques of nanotechnology and targeted drug delivery can go a long way in achieving the goal of One Health, which advocates the unity of multiple practices for the optimal health of people, animals, and the environment. Full article

Microbial biofilms present a formidable challenge in ophthalmology. Their intrinsic resistance to antibiotics and evasion of host immune defenses significantly complicate treatments for ocular infections such as conjunctivitis, keratitis, blepharitis, and endophthalmitis. These infections are often caused by pathogens, including Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, particularly in patients using contact lenses or intraocular implants—devices that serve as surfaces for biofilm formation. The global rise in antimicrobial resistance has intensified the search for alternative treatment modalities. In this regard, plant-derived antimicrobials have emerged as promising candidates demonstrating broad-spectrum antimicrobial and antibiofilm activity through different mechanisms from those of conventional antibiotics. These mechanisms include inhibiting quorum sensing, disrupting established biofilm matrices, and interfering with microbial adhesion and communication. However, the clinical translation of phytochemicals faces significant barriers, including variability in chemical composition due to environmental and genetic factors, difficulties in standardization and reproducibility, poor water solubility and ocular bioavailability, and a lack of robust clinical trials evaluating their efficacy and safety in ophthalmic settings. Furthermore, regulatory uncertainties and the absence of unified guidelines for approving plant-derived formulations further hinder their integration into evidence-based ophthalmic practice. This review synthesizes the current knowledge on the pathogenesis and treatment of biofilm-associated ocular infections, critically evaluating plant-based antimicrobials as emerging therapeutic agents. Notably, resveratrol, curcumin, abietic acid, and selected essential oils demonstrated notable antibiofilm activity against S. aureus, P. aeruginosa, and C. albicans. These findings support the potential of phytochemicals as adjunctive or alternative agents in managing biofilm-associated ocular infections. By highlighting both their therapeutic promise and translational limitations, this review contributes to the ongoing discourse on sustainable, innovative approaches to managing antibiotic-resistant ocular infections. Full article

The growing prevalence of bacterial infections and the alarming rise of antimicrobial resistance (AMR) have driven the need for innovative antimicrobial coatings for medical implants and biomaterials. However, implant surface properties, such as roughness, chemistry, and reactivity, critically influence biological interactions and must be engineered to ensure biocompatibility, corrosion resistance, and sustained antibacterial activity. This review evaluates three principal categories of antimicrobial agents utilized in surface functionalization: metal/metaloxide nanoparticles, antibiotics, and phytochemical compounds. Metal/metaloxide-based coatings, especially those incorporating silver (Ag), zinc oxide (ZnO), and copper oxide (CuO), offer broad-spectrum antimicrobial efficacy through mechanisms such as reactive oxygen species (ROS) generation and bacterial membrane disruption, with a reduced risk of resistance development. Antibiotic-based coatings enable localized drug delivery but often face limitations related to burst release, cytotoxicity, and diminishing effectiveness against multidrug-resistant (MDR) strains. In contrast, phytochemical-derived coatings—using bioactive plant compounds such as curcumin, eugenol, and quercetin—present a promising, biocompatible, and sustainable alternative. These agents not only exhibit antimicrobial properties but also provide anti-inflammatory, antioxidant, and osteogenic benefits, making them multifunctional tools for implant surface modification. The integration of these antimicrobial strategies aims to reduce bacterial adhesion, inhibit biofilm formation, and enhance tissue regeneration. By leveraging the synergistic effects of metal/metaloxide nanoparticles, antibiotics, and phytochemicals, next-generation implant coatings hold the potential to significantly improve infection control and clinical outcomes in implant-based therapies. Full article

This study aims to explore the potential repurposing of 5-fluorouridine (5-FUrd) as an antifungal agent against Candida species. We evaluated the responses of nine reference species of Candida spp. and one hundred clinical isolates of C. albicans to 5-FUrd using the broth microdilution method. Additionally, we assessed the effect of 5-FUrd on selected virulence factors, including biofilm formation, cell adhesion, dimorphism, hydrolase secretion, and hemolytic activity, in the two most sensitive Candida species, C. albicans and C. parapsilosis. The frequency of spontaneous mutations occurring in these two Candida species under the influence of 5-FUrd was also determined. Finally, we examined the cytotoxic properties of 5-FUrd against human erythrocytes and zebrafish embryos. Our results demonstrated that 5-FUrd exhibits antifungal activity in vitro, inhibits biofilm formation, suppresses hyphal growth, reduces cell surface hydrophobicity, eradicates mature biofilms, and decreases the secretion of extracellular proteinases and hemolytic activity in C. albicans and C. parapsilosis cells. The overall mutation frequency under the selective pressure of 5-FUrd ranged from 2 × 10⁻⁵ to 1.2 × 10⁻⁴ per species. Notably, the exposure to 5-FUrd did not induce significant toxic effects on human erythrocytes or zebrafish embryos. This study highlights the potential clinical application of 5-FUrd as an anti-Candida agent. Full article

Streptococcus pneumoniae (S. pneumoniae) Sortase A (SrtA) anchors virulence proteins to the surface of the cell wall by recognizing and cleaving the LPXTG motif. These toxins help bacteria adhere to and colonize host cells, promote biofilm formation, and trigger host inflammatory responses. Therefore, SrtA is an ideal target for the development of new preparations for S. pneumoniae. In this study, we found that phloretin (pht) and phlorizin (phz) exhibited excellent affinities for SrtA based on virtual screening experiments. We analyzed the interactive mechanism between pht, phz, and alnusone (aln, a reported S. pneumoniae SrtA inhibitor) and SrtA based on molecular dynamics simulation experiments. The results showed that these inhibitors bound to the active pocket of SrtA, and the root mean square deviation (RMSD) and distance analyses showed that these compounds and SrtA maintained stable configuration and binding during the assay. The binding free energy analysis showed that both electrostatic forces (ele), van der Waals forces (vdw), and hydrogen bonds (Hbonds) promoted the binding between pht, phz, and SrtA; however, for the binding of aln and SrtA, the vdw force was much stronger than ele, and Hbonds were not found. The binding free energy decomposition showed that HIS141, ILE143, and PHE119 contributed more energy to promote pht and SrtA binding; ARG215, ASP188, and LEU210 contributed more energy to promote phz and SrtA binding; and HIS141, ASP209, and ARG215 contributed more energy to promote aln and SrtA binding. Finally, the transpeptidase activity of SrtA decreased significantly when treated with different concentrations of pht, phz, or aln, which inhibited S. pneumoniae biofilm formation and adhesion to A549 cells without affecting normal bacterial growth. These results suggest that pht, phtz, and aln are potential materials for the development of novel inhibitors against S. pneumoniae infection. Full article

Marine biofouling, the process of marine microorganisms, algae, and invertebrates attaching to and forming biofilms on ship hulls, underwater infrastructure, and marine equipment in ocean environments, severely impacts shipping and underwater operations by increasing fuel consumption, maintenance costs, and corrosion risks, and by threatening marine ecosystem stability via invasive species transport. This study reports the development of a hydrogel-metal-organic framework (MOF)-quorum sensing inhibitor (QSI) antifouling coating on 304 stainless steel (SS) substrates. Inspired by mussel adhesion, a hydrophilic bionic hydrogel was first constructed via metal ion coordination. The traditional metal ion source was replaced with a zeolitic imidazolate framework-8 (ZIF-8) loaded with 2-(5H)-furanone (HF, a QSI) without altering coating formation. Physicochemical characterization using Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), the Brunauer–Emmett–Teller (BET) method, and the diffraction of x-rays (XRD) confirmed successful HF loading into ZIF-8 with intact crystal structures. Antifouling tests showed HF@ZIF-8 enhanced antibacterial inhibition against Staphylococcus aureus (97.28%) and Escherichia coli (>97%) and suppressed Chromobacterium violaceum CV026 pigment synthesis at 0.25 mg/mL (sub-growth concentration). The reconstructed PG/PVP/PEI/HF@ZIF-8 coating achieved 72.47% corrosion inhibition via synergistic anodic protection and physical shielding. This work provides a novel green approach for surface antifouling and drag reduction, highlighting MOF-loaded QSIs as promising additives to enhance the antifouling performance of hydrogel coatings, anti-corrosion performance, and QSI performance for sustainable marine engineering applications. Full article

Finding effective alternatives to antibiotics and zinc oxide in livestock feed remains challenging, but phytogenic compounds show promising potential. In the first part of the present study, the in vitro antimicrobial activities of carvacrol, eugenol, garlic oil, star anise oil, and tea tree oil as well as their effects on the biofilm formation of two Escherichia coli field isolates, quorum sensing of Chromobacterium violaceum, and the adhesion of an E. coli field isolate to piglets’ small intestinal mucus were determined. Based on these results, two prototypes were formulated. Phytogenic feed additive (PFA) Core 2, containing carvacrol, eugenol, and star anise oil, showed stronger in vitro antimicrobial activity, inhibition of biofilm formation, and quorum sensing than PFA Core 1, which was mainly composed of garlic oil and tea tree oil. In the second part of the present study, 1000 post-weaning piglets were divided into four groups receiving a control or diets with either PFA Core 1, PFA Core 2, or zinc oxide. Only PFA Core 2 and zinc oxide significantly improved body weight, daily gain, feed efficiency, and fecal scores compared with the control, while PFA Core 1 increased the feed efficiency and fecal scores. The results show that feed additives based on carvacrol and eugenol can improve the growth performance of post-weaning piglets and reduce the incidence of diarrhea, possibly by influencing detrimental bacteria. Furthermore, the present study demonstrates the potential of combinations of in vitro assays to support the development of effective feed additives. Full article

The incidence of fungal infections is significantly rising, posing a challenge due to the limited class of antifungal drugs. There is a necessity to combat emerging resistant fungal infections by developing novel antifungal agents. This study aimed to evaluate the antifungal effects of lawsone (LAW), a natural component extracted from herbal medicine, and LAW-loaded mesoporous silica nanoparticles (LAW-MSNs) on growth, biofilm formation, and expression of ALS1 and EPA1 genes contributing to cell adhesion of Candida spp. Twenty C. albicans and twenty C. glabrata isolates, including ten fluconazole-resistant and ten fluconazole-susceptible isolates, were examined. The findings of the study indicated that LAW and LAW-MSNs inhibited Candida isolates growth at MIC range of 0.31–>5 µg/mL and significantly reduced biofilm formation in C. albicans and C. glabrata. Moreover, both LAW and LAW-MSNs downregulated the expression of the adhesion genes ALS1 and EPA1 in C. albicans and C. glabrata. Based on the obtained findings, LAW emerged as a promising antifungal candidate. However, the nano-formulation (LAW-MSNs) improved its antifungal properties. Full article

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the human stomach and is associated with several gastric diseases, including gastritis, peptic ulcer disease, and gastric cancer. The bacterium’s ability to thrive in the harsh gastric environment is due, to some extent, to its stress response mechanisms, with its heat shock proteins (HSPs) playing a putative, yet not fully understood, role in these adaptive processes. HSPs are a family of molecules, highly conserved throughout phylogenesis, that assist in protein folding, prevent aggregation, and ensure cellular homeostasis under stressful conditions. In H. pylori, HSPs contribute to survival in the stomach’s acidic environment and oxidative stress. Furthermore, they aid in the bacterium’s ability to adhere to gastric epithelial cells, modulate the host immune response, and form biofilms, all contributing to chronic infection and pathogenicity. The role of microbial HSPs in antibiotic resistance has also emerged as a critical area of research, as these proteins help stabilize efflux pumps, protect essential proteins targeted by antibiotics, and promote biofilm formation, thereby reducing the efficacy of antimicrobial treatments. Among bacterial HSPs, GroEL and DnaK are probably the major proteins that control most of the H. pylori’s functioning. Indeed, both proteins possess remarkable acid resistance, high substrate affinity, and dual roles in protein homeostasis and host interaction. These features make them critical for H. pylori’s adaptation, persistence, and pathogenicity in the gastric niche. In addition, recent findings have also highlighted the involvement of HSPs in the crosstalk between H. pylori and gastric epithelial cells mediated by the release of bacterial outer membrane vesicles and host-derived exosomes, both of these extracellular vesicles being part of the muco-microbiotic layer of the stomach and influencing cellular signalling and immune modulation. Considering their critical role in the survival and persistence of bacteria, microbial HSPs also represent potential therapeutic targets. Strategies aimed at inhibiting microbial HSP function, combined with conventional antibiotics or developing vaccines targeting microbial HSPs, could provide new avenues for the treatment of H. pylori infections and combat antibiotic resistance. This review explores the multifaceted roles of microbial HSPs in the pathogenesis of H. pylori, highlighting their contributions to bacterial adhesion, immune evasion, stress response, and antibiotic resistance. Full article

Implant-associated infections (IAIs) are major complications in dental and orthopedic implants, potentially compromising osseointegration and eventually causing implant loosening or removal. Thus, early prevention of bacterial adhesion and biofilm formation is critical for successful long-term osseointegration. Polyetheretherketone (PEEK) exhibits excellent physicochemical properties and an elastic modulus similar to bone tissue, making it a promising material for dental and orthopedic implants. However, its inherent lack of antibacterial properties limits its ability to prevent IAIs. Herein, an antibacterial coating with controlled drug release and excellent biocompatibility is designed by immobilizing minocycline (Mino)-doped carboxymethyl chitosan (CMCS) onto the PEEK surface via a polydopamine (PDA)-mediated Michael addition and Schiff base reaction. The coating is characterized by SEM, XPS, water contact angle measurements, and in vitro Mino release assays. Antibacterial activity is evaluated using the zone of inhibition (ZOI), turbidity, and colony counting assays, while biocompatibility is assessed through a SEM analysis of cell morphology and CCK-8 assay. The results show that the Mino-modified coating is successfully fabricated on the PEEK surface, achieving sustained Mino release for up to 14 days. Among the three Mino concentrations, the PEEK-0.5Mino group demonstrates the best balance of antibacterial activity and biocompatibility, highlighting its potential for preventing IAIs in orthopedic and dental applications. Full article

Increasing antifungal resistance and side effects of existing drugs demand alternative approaches for treating Candida (C.) infections. This study aimed to comprehensively evaluate the antifungal efficacy of myricetin (MYR), a natural flavonoid, against both fluconazole (FLC)-resistant and susceptible clinical Candida strains, with a particular focus on its inhibitory effects on C. albicans biofilms. Antifungal susceptibility was evaluated on Candida spp. by the broth microdilution method, and the impact of myricetin on C. albicans biofilms was determined using the Cell Counting Kit-8 (CCK-8) assay. To understand the molecular mechanisms underlying the antibiofilm properties of myricetin, expression analysis of genes in the RAS1/cAMP/EFG1 pathway (ALS3, HWP1, ECE1, UME6, HGC1) and cAMP-dependent protein kinase regulation (RAS1, CYR1, EFG1) involved in the transition from yeast to hyphae was performed. Field emission scanning electron microscopy (FESEM) was used to study the ultrastructural changes and morphological dynamics of Candida biofilms after exposure to MYR and FLC. The in vivo toxicity of myricetin was evaluated by survival analysis using the Galleria mellonella model. Myricetin significantly suppressed key genes related to hyphae development (RAS1, CYR1, EFG1, UME6, and HGC1) and adhesion (ALS3 and HWP1) in both clinical and reference Candida strains at a concentration of 640 µg/mL. FESEM analysis revealed that myricetin inhibited hyphae growth and elongation in C. albicans. This study highlights the promising antibiofilm potential of myricetin through a significant inhibition of biofilm formation and hyphal morphogenesis. Full article

Precise separation and antifouling capabilities are critical for the application of membrane separation technology. In this work, we developed a multiplayer layer-by-layer assembly strategy to sequentially deposit tannic acid (TA) and lysozyme (Lys) onto polyethersulfone/iron (PES/Fe) ultrafiltration membrane substrates, enabling the simple and efficient fabrication of a biofouling-resistant loose nanofiltration (LNF) membrane with superior dye/salt separation performance. This approach fully leverages the multifunctionality of TA by exploiting its coordination with Fe³⁺ and non-covalent interactions with Lys. The obtained PES/Fe-TA-Lys LNF membrane exhibits a pure water flux of 57.5 L·m⁻²·h⁻¹, along with exceptional dye rejection rates (98.3% for Congo Red (CR), 99.2% for Methyl Blue (MB), 98.4% for Eriochrome Black T (EBT), and 67.6% for Acid Orange 74 (AO74)) while maintaining minimal salt retention (8.2% for Na₂SO₄, 4.3% for MgSO₄, 3.5% for NaCl, and 2.4% for MgCl₂). The PES/Fe-TA-Lys LNF membrane also displays outstanding antifouling performance against bovine serum albumin (BSA), humic acid (HA), and CR, along with strong biofouling resistance against Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) via synergistic anti-adhesion and biofilm inhibiting effects. This work presents a novel and scalable approach to fabricating biofouling-resistant LNF membranes, offering great potential for dye/salt separation in textile wastewater treatment. Full article

Ocular fungal infections are slow-progressing conditions that primarily affect the cornea but can also involve the entire eyeball. Candida albicans is one of the most involved species. Both diagnosing and treating these infections require prompt and effective action. However, the currently available treatment options mainly rely on azoles and polyenes, which are known for their poor penetration into ocular tissue and associated toxicity. Moreover, conventional antifungals are usually ineffective when tested against biofilm-associated infections, mainly due to the metabolically inactive state of dormant cells embedded in the extracellular biofilm matrix. Here, analysis of the in vitro antifungal activity of four 2-aminobenzoic acid derivatives synthesized using a green method and their combination with Fluconazole (FLC) showed efficacy against the FLC-resistant clinical isolate of C. albicans under both planktonic and biofilm formation conditions. Results showed that compounds 1 and 2 exhibited the best antifungal activity in the checkerboard association test, presenting a synergistic effect towards antifungal action. The downregulation of HWP, ERG11, and ASL3 genes during biofilm inhibition suggested a reduced capacity of the four compounds for hyphal growth and adhesion, as well as a decrease in pathogenicity due to the downregulation of some SAP genes. In vitro and in vivo toxicity profiles indicated that these compounds exhibited low toxicity, as well as the absence of genotoxic effects. Therefore, green-synthetized 2-aminobenzoic acid derivatives may have potential as antifungal agents for the inhibition of C. albicans growth and biofilm formation. Full article