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Search Results (434)

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Keywords = novel biofilm treatments

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19 pages, 1579 KiB  
Article
Plasma-Treated Water Effect on Sporulating Bacillus cereus vs. Non-Sporulating Listeria monocytogenes Biofilm Cell Vitality
by Samantha Nestel, Robert Wagner, Mareike Meister, Thomas Weihe and Uta Schnabel
Appl. Microbiol. 2025, 5(3), 80; https://doi.org/10.3390/applmicrobiol5030080 - 5 Aug 2025
Abstract
Foodborne illness caused by bacterial pathogens is a global health concern and results in millions of infections annually. Therefore, food products typically undergo several processing stages, including sanitation steps, before being distributed in an attempt to remove pathogens. However, many sanitation methods have [...] Read more.
Foodborne illness caused by bacterial pathogens is a global health concern and results in millions of infections annually. Therefore, food products typically undergo several processing stages, including sanitation steps, before being distributed in an attempt to remove pathogens. However, many sanitation methods have compounding effects on the color, texture, flavor, and nutritional quality of the product or do not effectively reduce the pathogens that food can be exposed to. Some bacterial pathogens particularly possess traits and tactics that make them even more difficult to mitigate such as biofilm formation. Non-thermal plasma sanitation techniques, including plasma-treated water (PTW), have proven to be promising methods that significantly reduce pathogenic bacteria that food is exposed to. Published work reveals that PTW can effectively mitigate both gram-positive and gram-negative bacterial biofilms. This study presents a novel analysis of the differences in antimicrobial effects of PTW treatment between biofilm-forming gram-positive bacteria, commonly associated with foodborne illness, that are sporulating (Bacillus cereus) and non-sporulating (Listeria monocytogenes). After treatment with PTW, the results suggest the following hypotheses: (1) that the non-sporulating species experiences less membrane damage but a greater reduction in metabolic activity, leading to a possible viable but non-culturable (VBNC) state, and (2) that the sporulating species undergoes spore formation, which may subsequently convert into vegetative cells over time. PTW treatment on gram-positive bacterial biofilms that persist in food processing environments proves to be effective in reducing the proliferating abilities of the bacteria. However, the variance in PTW’s effects on metabolic activity and cell vitality between sporulating and non-sporulating species suggest that other survival tactics might be induced. This analysis further informs the application of PTW in food processing as an effective sanitation method. Full article
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21 pages, 6211 KiB  
Article
In Silico and In Vitro Potential Antifungal Insights of Insect-Derived Peptides in the Management of Candida sp. Infections
by Catarina Sousa, Alaka Sahoo, Shasank Sekhar Swain, Payal Gupta, Francisco Silva, Andreia S. Azevedo and Célia Fortuna Rodrigues
Int. J. Mol. Sci. 2025, 26(15), 7449; https://doi.org/10.3390/ijms26157449 - 1 Aug 2025
Viewed by 242
Abstract
The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the [...] Read more.
The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the target-specific binding efficacy of insect-derived antifungal peptides (n = 37) as possible alternatives to traditional antifungal treatments. Using computational methods, namely the HPEPDOCK and HDOCK platforms, molecular docking was performed to evaluate the interactions between selected key fungal targets, lanosterol 14-demethylase, or LDM (PDB ID: 5V5Z), secreted aspartic proteinase-5, or Sap-5 (PDB ID: 2QZX), N-myristoyl transferase, or NMT (PDB ID: 1NMT), and dihydrofolate reductase, or DHFR, of C. albicans. The three-dimensional peptide structure was modelled through the PEP-FOLD 3.5 tool. Further, we predicted the physicochemical properties of these peptides through the ProtParam and PEPTIDE 2.0 tools to assess their drug-likeness and potential for therapeutic applications. In silico results show that Blap-6 from Blaps rhynchopeter and Gomesin from Acanthoscurria gomesiana have the most antifungal potential against all four targeted proteins in Candida sp. Additionally, a molecular dynamics simulation study of LDM-Blap-6 was carried out at 100 nanoseconds. The overall predictions showed that both have strong binding abilities and are good candidates for drug development. In in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. C. tropicalis demonstrated relative resistance to complete eradication by both peptides. The present study provides evidence to support the antifungal activity of certain insect peptides, with potential to be used as alternative drugs or as a template for a new synthetic or modified peptide in pursuit of effective therapies against Candida spp. Full article
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23 pages, 3832 KiB  
Article
Novel Probiotic Strain Lactiplantibacillus plantarum CNTA 628 Modulates Lipid Metabolism and Improves Healthspan in C. elegans
by Ignacio Goyache, Lorena Valdés-Varela, Raquel Virto, Miguel López-Yoldi, Noelia López-Giral, Ana Sánchez-Vicente, Fermín I. Milagro and Paula Aranaz
Appl. Sci. 2025, 15(14), 8007; https://doi.org/10.3390/app15148007 - 18 Jul 2025
Viewed by 308
Abstract
The call for new approaches to prevent and treat metabolic syndrome-related diseases has led to research on the use of lacto-fermentative probiotics with beneficial metabolic properties like Lactobacilli. Here, we characterize the probiotic properties of a novel strain, Lactiplantibacillus plantarum CNTA 628, [...] Read more.
The call for new approaches to prevent and treat metabolic syndrome-related diseases has led to research on the use of lacto-fermentative probiotics with beneficial metabolic properties like Lactobacilli. Here, we characterize the probiotic properties of a novel strain, Lactiplantibacillus plantarum CNTA 628, and investigate its potential anti-obesity and health-promoting activities in the Caenorhabditis elegans model, additionally elucidating the molecular mechanisms involved. Lactiplantibacillus plantarum CNTA 628 exhibited sensitivity to the entire spectrum of antibiotics analyzed, gastric and intestinal resistance in vitro, β-galactosidase and bile-salt hydrolysate activities, and the capacity to form biofilms and produce SCFAs. In addition, it reduced the binding of the pathogenic E. coli O157:H7 to intestinal epithelial cells (Caco-2) and exerted immune-modulating effects in cellular models. Supplementation with this probiotic significantly reduced C. elegans fat accumulation by more than 18% under control and high-glucose conditions, lowered senescence, improved oxidative stress, and significantly enhanced lifespan without affecting the development of the worms. Gene expression analyses evidenced that L. plantarum CNTA 628 plays a role in regulating daf-22 and maoc-1 gene expression, both linked to beta-oxidation pathways. Our results demonstrate the health-benefiting properties of this novel strain and suggest its potential as probiotic candidate for the prevention and treatment of metabolic syndrome-related conditions. Full article
(This article belongs to the Special Issue Probiotics, Prebiotics, Postbiotics: From Mechanisms to Applications)
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32 pages, 2479 KiB  
Review
Fungal Biofilm: An Overview of the Latest Nano-Strategies
by Andrea Giammarino, Laura Verdolini, Giovanna Simonetti and Letizia Angiolella
Antibiotics 2025, 14(7), 718; https://doi.org/10.3390/antibiotics14070718 - 17 Jul 2025
Viewed by 589
Abstract
Background/Objectives: There is an increasing incidence of fungal infections in conjunction with the rise in resistance to medical treatment. Antimicrobial resistance is frequently associated with virulence factors such as adherence and the capacity of biofilm formation, which facilitates the evasion of the [...] Read more.
Background/Objectives: There is an increasing incidence of fungal infections in conjunction with the rise in resistance to medical treatment. Antimicrobial resistance is frequently associated with virulence factors such as adherence and the capacity of biofilm formation, which facilitates the evasion of the host immune response and resistance to drug action. Novel therapeutic strategies have been developed to overcome antimicrobial resistance, including the use of different type of nanomaterials: metallic (Au, Ag, Fe3O4 and ZnO), organic (e.g., chitosan, liposomes and lactic acid) or carbon-based (e.g., quantum dots, nanotubes and graphene) materials. The objective of this study was to evaluate the action of nanoparticles of different synthesis and with different coatings on fungi of medical interest. Methods: Literature research was conducted using PubMed and Google Scholar databases, and the following terms were employed in articles published up to June 2025: ‘nanoparticles’ in combination with ‘fungal biofilm’, ‘Candida biofilm’, ‘Aspergillus biofilm’, ‘Cryptococcus biofilm’, ‘Fusarium biofilm’ and ‘dermatophytes biofilm’. Results: The utilization of nanoparticles was found to exert a substantial impact on the reduction in fungal biofilm, despite the presence of substantial variability in minimum inhibitory concentration (MIC) values attributable to variations in nanoparticle type and the presence of capping agents. It was observed that the MIC values were lower for metallic nanoparticles, particularly silver, and for those synthesized with polylactic acid compared to the others. Conclusions: Despite the limited availability of data concerning the stability and biocompatibility of nanoparticles employed in the treatment of fungal biofilms, it can be posited that these results constitute a significant initial step. Full article
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14 pages, 1987 KiB  
Article
The Characterization of a Gonococcal HicAB Toxin–Antitoxin System Capable of Causing Bacteriostatic Growth Arrest
by Salwa S. Bagabas, Jorge Trujillo-Mendoza, Michael J. Stocks, David P. J. Turner and Neil J. Oldfield
Microorganisms 2025, 13(7), 1619; https://doi.org/10.3390/microorganisms13071619 - 9 Jul 2025
Viewed by 515
Abstract
Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection gonorrhea. Preventative vaccines or novel treatments based on a better understanding of the molecular basis of N. gonorrhoeae infection are required as resistance to current antibiotics is widespread. Toxin–antitoxin (TA) systems modulate [...] Read more.
Neisseria gonorrhoeae is the causative agent of the sexually transmitted infection gonorrhea. Preventative vaccines or novel treatments based on a better understanding of the molecular basis of N. gonorrhoeae infection are required as resistance to current antibiotics is widespread. Toxin–antitoxin (TA) systems modulate bacterial physiology by interfering with vital cellular processes; type II TA systems, where both toxin and antitoxin are proteins, are the best-studied. Bioinformatics analysis revealed genes encoding an uncharacterized type II HicAB TA system in the N. gonorrhoeae strain FA1090 chromosome, which were also present in >83% of the other gonococcal genome sequences examined. Gonococcal HicA overproduction inhibited bacterial growth in Escherichia coli, an effect that could be counteracted by the co-expression of HicB. Kill/rescue assays showed that this effect was bacteriostatic rather than bactericidal. The site-directed mutagenesis of key histidine and glycine residues (Gly22, His24, His29) abolished HicA-mediated growth arrest. N. gonorrhoeae FA1090∆hicAB and complemented derivatives that expressed IPTG-inducible hicA, hicB, or hicAB, respectively, grew as wild type, except for IPTG-induced FA1090∆hicAB::hicA. RT-PCR demonstrated that hicAB are transcribed in vitro under the culture conditions used. The deletion of hicAB had no effect on biofilm formation. Our study describes the first characterization of a HicAB TA system in N. gonorrhoeae. Full article
(This article belongs to the Section Molecular Microbiology and Immunology)
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22 pages, 2428 KiB  
Article
Assessment of Metabolic Alterations Induced by Halogenated Additives and Antifungal Activity of Extracts from the Endophytic Fungus Fusarium sp. Associated with Dizygostemon riparius (Plantaginaceae)
by Hilzimar de Jesus Freitas Sá, Anne Karoline Maiorana Santos, Adriano Souza Fonseca, Lourivaldo da Silva Santos, Josivan Regis Farias, Rosane Nassar Meireles Guerra, Edson Rodrigues-Filho, Gilmar Silverio da Silva, Cleydlenne Costa Vasconcelos, Alberto Jorge Oliveira Lopes and Antônio José Cantanhede Filho
Metabolites 2025, 15(7), 451; https://doi.org/10.3390/metabo15070451 - 4 Jul 2025
Viewed by 358
Abstract
Background/Objectives: Endophytic fungi are valuable sources of bioactive compounds with potential therapeutic applications. This study aimed to evaluate the antifungal activity of secondary metabolites produced by Fusarium sp. isolated from Dizygostemon riparius, with particular focus on the impact of culture medium [...] Read more.
Background/Objectives: Endophytic fungi are valuable sources of bioactive compounds with potential therapeutic applications. This study aimed to evaluate the antifungal activity of secondary metabolites produced by Fusarium sp. isolated from Dizygostemon riparius, with particular focus on the impact of culture medium supplementation with halogenated and metallic additives on metabolite production. Methods: The fungus was cultivated in standard Czapek medium and media supplemented with NH4Br or MnCl2. Methanolic extracts were obtained, fractionated, and chemically characterised via LC-ESI-HRMS. In vitro antifungal assays, including MIC and MFC determinations and biofilm inhibition tests, were performed against Candida albicans strains. In vivo toxicity and efficacy were assessed using Tenebrio molitor larvae. Results: Fifteen metabolites were annotated, including known antifungals such as fusaric acid and cyclosporin A. Fractions EMBr4 and EMC5 demonstrated fungicidal activity with MIC values close to fluconazole and significantly inhibited biofilm formation and maturation. In vivo, these fractions displayed low acute toxicity and improved survival in infected larvae, comparable to fluconazole treatment. Conclusions: The results indicate that culture medium modulation enhances the production of bioactive metabolites by Fusarium sp., leading to extracts with notable antifungal efficacy and safety. EMBr4 and EMC5 are promising candidates for further development as antifungal agents, particularly for targeting biofilm-associated Candida infections. These findings support the potential of endophytic fungi as sources of novel therapeutics and warrant further mechanistic and pharmacological investigations. Full article
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19 pages, 3483 KiB  
Article
Preparation of CF-NiO-PANI Electrodes and Study on the Efficiency of MFC in Recovering Potato Starch Wastewater
by Yiwei Han, Jingyuan Wang, Liming Jiang, Jiuming Lei, Wenjing Li, Tianyi Yang, Zhijie Wang, Jinlong Zuo and Yuyang Wang
Coatings 2025, 15(7), 776; https://doi.org/10.3390/coatings15070776 - 30 Jun 2025
Viewed by 268
Abstract
Microbial Fuel Cell (MFC) is a novel bioelectrochemical system that catalyzes the oxidation of chemical energy in organic waste and converts it directly into electrical energy through the attachment and growth of electroactive microorganisms on the electrode surface. This technology realizes the synergistic [...] Read more.
Microbial Fuel Cell (MFC) is a novel bioelectrochemical system that catalyzes the oxidation of chemical energy in organic waste and converts it directly into electrical energy through the attachment and growth of electroactive microorganisms on the electrode surface. This technology realizes the synergistic effect of waste treatment and renewable energy production. A CF-NiO-PANI capacitor composite anode was prepared by loading polyaniline on a CF-NiO electrode to improve the capacitance of a CF electrode. The electrochemical characteristics of the composite anode were evaluated using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), and the electrode materials were analyzed comprehensively by scanning electron microscopy (SEM), energy diffusion spectrometer (EDS), and Fourier transform infrared spectroscopy (FTIR). MFC system based on CF-NiO-PANI composite anode showed excellent energy conversion efficiency in potato starch wastewater treatment, and its maximum power density increased to 0.4 W/m3, which was 300% higher than that of the traditional CF anode. In the standard charge–discharge test (C1000/D1000), the charge storage capacity of the composite anode reached 2607.06 C/m2, which was higher than that of the CF anode (348.77 C/m2). Microbial community analysis revealed that the CF-NiO-PANI anode surface formed a highly efficient electroactive biofilm dominated by electrogenic bacteria (accounting for 47.01%), confirming its excellent electron transfer ability. The development of this innovative capacitance-catalytic dual-function anode material provides a new technical path for the synergistic optimization of wastewater treatment and energy recovery in MFC systems. Full article
(This article belongs to the Section Environmental Aspects in Colloid and Interface Science)
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25 pages, 1218 KiB  
Review
Probiotics in Nanotechnology-Driven Wound Healing: From Mechanistic Insight to Clinical Promise
by Milind Umekar, Anis Ahmad Chaudhary, Monali Manghani, Supriya Shidhaye, Pratiksha Khajone, Jayashri Mahore, Hassan Ahmad Rudayni and Rashmi Trivedi
Pharmaceutics 2025, 17(7), 805; https://doi.org/10.3390/pharmaceutics17070805 - 21 Jun 2025
Viewed by 1137
Abstract
Chronic wounds, including diabetic foot ulcers and pressure sores, are becoming more prevalent due to aging populations and increased metabolic problems. These wounds often persist due to impaired healing, chronic inflammation, oxidative stress, and infections caused by multidrug-resistant pathogens, making conventional treatments—including antibiotics [...] Read more.
Chronic wounds, including diabetic foot ulcers and pressure sores, are becoming more prevalent due to aging populations and increased metabolic problems. These wounds often persist due to impaired healing, chronic inflammation, oxidative stress, and infections caused by multidrug-resistant pathogens, making conventional treatments—including antibiotics and antiseptics—largely inadequate. This creates an urgent need for advanced, biologically responsive therapies that can both combat infection and promote tissue regeneration. Probiotics have surfaced as a viable option owing to their capacity to regulate immune responses, impede pathogenic biofilms, and generate antibacterial and antioxidant metabolites. However, their clinical application is limited by poor viability, sensitivity to environmental conditions, and short retention at wound sites. Nanotechnology-based delivery systems address these limitations by protecting probiotics from degradation, enhancing site-specific delivery, and enabling controlled, stimuli-responsive release. Encapsulation techniques using materials like chitosan, PLGA, liposomes, nanogels, nanofibers, and microneedles have shown significant success in improving wound healing outcomes in preclinical and clinical models. This review summarizes the current landscape of chronic wound challenges and presents recent advances in probiotic-loaded nanotechnologies. It explores various nano-delivery systems, their mechanisms of action, biological effects, and therapeutic outcomes, highlighting the synergy between probiotics and nanocarriers as a novel, multifaceted strategy for managing chronic wounds. Full article
(This article belongs to the Topic Probiotics: New Avenues)
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16 pages, 3913 KiB  
Article
Isolation and Characterization of Enterococcus faecalis Phage ZXL-01 and Preliminary Investigation of Its Therapeutic Effect on Periapical Periodontitis
by Hailin Jiang, Xueli Zhao, Chuhan Wang, Hongyan Shi, Jinghua Li, Chunyan Zhao and Honglan Huang
Curr. Issues Mol. Biol. 2025, 47(6), 469; https://doi.org/10.3390/cimb47060469 - 18 Jun 2025
Viewed by 388
Abstract
Enterococcus faecalis (E. faecalis) is a major pathogen responsible for refractory apical periodontitis (RAP). It can penetrate deep into dentinal tubules, form persistent biofilms, and exhibit antibiotic resistance, thereby limiting the efficacy of conventional antimicrobial treatments. Bacteriophages (phages), due to their [...] Read more.
Enterococcus faecalis (E. faecalis) is a major pathogen responsible for refractory apical periodontitis (RAP). It can penetrate deep into dentinal tubules, form persistent biofilms, and exhibit antibiotic resistance, thereby limiting the efficacy of conventional antimicrobial treatments. Bacteriophages (phages), due to their strong lytic activity and host specificity, have emerged as promising alternatives. In this study, a novel strictly lytic phage, ZXL-01, was isolated from lake water in Jilin, China. ZXL-01 demonstrated remarkable stability under extreme conditions, including thermal tolerance at 60 °C for 1 h and a wide pH range (4–11). Whole-genome sequencing (GenBank accession number: ON113334) revealed a genome of 40,804 bp with no virulence or tRNA genes, confirming its identity as an E. faecalis phage. Importantly, ZXL-01 exhibited potent antibiofilm activity, reducing biofilm biomass by approximately 69.4% in the inhibition group and 68.4% in the lysis group (both p < 0.001). In an in vitro root canal infection model induced by E. faecalis, scanning electron microscope (SEM) observations confirmed that ZXL-01 effectively inhibited biofilm formation and disrupted mature biofilms. These findings highlight the potential of ZXL-01 as a novel antimicrobial agent for the treatment of E. faecalis-associated apical periodontitis. Full article
(This article belongs to the Section Molecular Microbiology)
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22 pages, 7420 KiB  
Article
The Novel iMPACT Tool and Quadrant Protocol for Peri-Implantitis: Surface Refinement and Re-Osseointegration Validated by SEM/EDS and Long-Term Clinical Case Reports
by Gustavo Vicentis Oliveira Fernandes, Bruno Gomes dos Santos Martins, Juliana Campos Hasse Fernandes, Yankel Gabet and Amiram Vizanski
Medicina 2025, 61(6), 1094; https://doi.org/10.3390/medicina61061094 - 16 Jun 2025
Viewed by 737
Abstract
Background and Objectives: The goal of this study was to introduce a novel device, the iMPACT implant planer, designed to machine (create a complete smooth surface) contaminated implant surfaces intraorally, promoting peri-implant tissue healing and possible re-osseointegration, and the new Quadrant protocol, [...] Read more.
Background and Objectives: The goal of this study was to introduce a novel device, the iMPACT implant planer, designed to machine (create a complete smooth surface) contaminated implant surfaces intraorally, promoting peri-implant tissue healing and possible re-osseointegration, and the new Quadrant protocol, evaluating them in vitro and clinically. The null hypothesis was that there would be no improvement in the clinical parameters for the implants with peri-implantitis (PI) treated with the new protocol and tool. Materials and Methods: The Quadrant protocol was used in conjunction with the iMPACT tool, which primarily functions to remove biofilm and microbial contaminants from the exposed implant surface, while simultaneously preparing the surface through standardized implantoplasty, thereby enhancing the potential for re-osseointegration. An in vitro analysis was developed, and three medium/long-term cases were presented, detailing the procedures and outcomes. Results: The in vitro assessment showed smooth surfaces after treatment. Different areas presented minimal particles (<1 μm) on the implant surface, with a high content of titanium (Ti) and tungsten (W). In case 1, severe and advanced peri-implantitis around implants #46 and #47 was found. A combination of resective (Quadrant + iMPACT) and regenerative surgery was used for treatment, along with a buccal single flap (BSF). Significant clinical and radiographic improvements were observed at 14 and 43 months postoperatively, including vertical bone gain with re-osseointegration and stable probing depths (PDs). In the second case, a severe PI and prosthesis instability were observed. Resective (Quadrant + iMPACT) and regenerative procedures were applied. At 3 and 12 months postoperatively, clinical and radiographic evaluations demonstrated significant improvements with re-osseointegration, including PDs reduced to 0–1 mm and a vertical bone gain of approximately 6.5 mm. In case 3, mandibular implants from 42 to 47 exhibited inflammation, suppuration, and moderate-to-severe bone loss. Just resective surgery (Quadrant + iMPACT), without grafting, was performed. At 6- and 12-month follow-ups, clinical and radiographic assessments showed the resolution of inflammation, stable bone levels, and healthy peri-implant gingiva. Conclusions: Favorable outcomes were achieved using the iMPACT and Quadrant protocols in the three clinical cases, resulting in re-osseointegration when combined with regenerative procedures. The favorable medium/long-term outcomes achieved, despite the patient’s complex medical history and, at times, inconsistent oral hygiene, underscore the potential efficacy of such interventions. Full article
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18 pages, 2527 KiB  
Article
Targeting Azole-Resistant Candida albicans: Tetrapeptide Tuftsin-Modified Liposomal Vaccine Induces Superior Immune Protection
by Masood A. Khan, Arif Khan, Abdullah M. Alnuqaydan, Aqel Albutti, Basmah F. Alharbi and Mohammad Owais
Vaccines 2025, 13(6), 630; https://doi.org/10.3390/vaccines13060630 - 11 Jun 2025
Viewed by 999
Abstract
Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential [...] Read more.
Background/objectives: Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential of a new liposomal vaccine formulation, Tuft-lip-WCAgs, comprising Tuftsin and C. albicans whole cell antigens, in providing immune protection against systemic candidiasis. Methods: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-γ and IL-4) from splenocytes. Results: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 ± 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 ± 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-γ (634 ± 128 pg/mL) and IL-4 (582 ± 82 pg/mL), indicating a balanced Th1/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 ± 197 CFUs/g). Conclusions: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis. Full article
(This article belongs to the Special Issue Peptide-Based Vaccines)
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21 pages, 3126 KiB  
Article
Phage–Antibiotic Synergy Enhances Biofilm Eradication and Survival in a Zebrafish Model of Pseudomonas aeruginosa Infection
by Ling-Chun Lin, Yu-Chuan Tsai and Nien-Tsung Lin
Int. J. Mol. Sci. 2025, 26(11), 5337; https://doi.org/10.3390/ijms26115337 - 1 Jun 2025
Viewed by 804
Abstract
Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that poses a significant threat due to its increasing multidrug resistance, particularly in clinical settings. This study aimed to isolate and characterize a novel bacteriophage, phiLCL12, from hospital wastewater and evaluate its potential in combination with [...] Read more.
Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that poses a significant threat due to its increasing multidrug resistance, particularly in clinical settings. This study aimed to isolate and characterize a novel bacteriophage, phiLCL12, from hospital wastewater and evaluate its potential in combination with antibiotics to combat P. aeruginosa infections and biofilm formation. Transmission electron microscopy revealed that phiLCL12 possesses a long contractile tail. The isolated phage exhibited a broad host range of 82.22% and could adsorb up to 98% of its target within 4 min. It was effective against multidrug-resistant strains at both high and low multiplicities of infection (MOIs) levels in lysis tests. Taxonomic classification was determined using PhaGCN2 and Whole genomic analysis, and the results identified phiLCL12 as a member of the Pbunavirus. In vitro experiments demonstrated that phiLCL12 significantly enhanced biofilm clearance and inhibited biofilm formation when combined with sub-inhibitory concentrations of imipenem. Furthermore, in vivo experiments using a zebrafish model showed that phage–antibiotic synergy (PAS) improved survival rate compared to antibiotic treatment alone. This study demonstrates that phiLCL12 is effective in both eradicating and preventing P. aeruginosa biofilm formation. The combination of phiLCL12 and imipenem provides a synergistic effect, significantly enhancing survival outcomes in a zebrafish model. These findings highlight the potential of phage–antibiotic synergy as a promising therapeutic strategy against biofilm-associated infections. Full article
(This article belongs to the Collection Feature Papers in Molecular Immunology)
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18 pages, 2647 KiB  
Article
The Synthesis and Biological Evaluation of a Novel Pleuromutilin Derivative Containing a 4-Fluorophenyl Group Targeting MRSA
by Yongfei Wang, Yi Zhao, Haiting Wang, Bo Liu, Shuangyi Zhang, Yuan Liu, Ruinan Li, Tao Zhang, Surong Hasi and Wei Mao
Molecules 2025, 30(11), 2366; https://doi.org/10.3390/molecules30112366 - 29 May 2025
Viewed by 560
Abstract
The pleuromutilin derivative, the compound PL-W, was synthesized by introducing a 4-fluorophenyl group at the C21 position and selected for comprehensive antibacterial evaluation. PL-W demonstrated notable antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 0.03125 µg/mL, which [...] Read more.
The pleuromutilin derivative, the compound PL-W, was synthesized by introducing a 4-fluorophenyl group at the C21 position and selected for comprehensive antibacterial evaluation. PL-W demonstrated notable antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 0.03125 µg/mL, which is significantly lower than that of tiamulin (0.5 µg/mL). Crystal violet (CV) staining revealed that it inhibited MRSA biofilm formation and electron microscopy revealed that it disrupted bacterial cell division and, possibly, the synthesis of essential cell wall proteins. In both in vivo models, PL-W exhibited excellent performance. In the Galleria mellonella infection model, treatment with different concentrations of PL-W increased the survival rate from 20% to 90% and significantly reduced the bacterial load. In the mouse model of MRSA pneumonia, a 10 mg/kg dose of PL-W increased the survival rate to 70%, decreased the bacterial load in the lungs, and alleviated inflammatory damage. Molecular docking studies indicated that PL-W had a similar docking pose and comparable binding affinity to that of lefamulin, with hydrogen bond interactions that are crucial for binding to the peptidyl transferase center (PTC). Moreover, it demonstrated no significant reduction in cell viability in HepG2 and HEK293 cells, even at high concentrations (≤50 µg/mL). Overall, PL-W shows significant potential as a novel anti-MRSA agent owing to its potent in vitro and in vivo activities and low cytotoxicity. Full article
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18 pages, 671 KiB  
Review
Evaluating the Efficacy of Rose Bengal as a Photosensitizer in Antimicrobial Photodynamic Therapy Against Candida albicans: A Systematic Review
by Jakub Fiegler-Rudol, Barbara Lipka, Katarzyna Kapłon, Magdalena Moś, Dariusz Skaba, Aleksandra Kawczyk-Krupka and Rafał Wiench
Int. J. Mol. Sci. 2025, 26(11), 5034; https://doi.org/10.3390/ijms26115034 - 23 May 2025
Viewed by 784
Abstract
Candida albicans is a significant pathogen in various fungal infections, including oral candidiasis and denture stomatitis. As antifungal resistance rises globally, there is an urgent need for alternative treatment strategies. Antimicrobial photodynamic therapy (aPDT), utilizing a photosensitizer and light to produce reactive oxygen [...] Read more.
Candida albicans is a significant pathogen in various fungal infections, including oral candidiasis and denture stomatitis. As antifungal resistance rises globally, there is an urgent need for alternative treatment strategies. Antimicrobial photodynamic therapy (aPDT), utilizing a photosensitizer and light to produce reactive oxygen species (ROS), has emerged as a promising approach. Rose Bengal (RB), a xanthene dye, exhibits a high singlet oxygen quantum yield, making it a candidate for aPDT. However, its efficacy in C. albicans treatment has been inconsistent, particularly against biofilm-associated infections, which are more resistant to conventional therapies. This systematic review evaluates the efficacy of Rose Bengal-mediated aPDT in combating C. albicans infections by synthesizing data from studies conducted over the past decade. We focus on the effectiveness of RB across different experimental conditions, including planktonic and biofilm forms of C. albicans. The review also explores the synergy between RB and other agents, such as potassium iodide, and compares the outcomes of RB-mediated aPDT to other photosensitizers and conventional antifungal treatments. Despite its potential, RB-aPDT shows variable effectiveness due to differences in experimental protocols, such as the photosensitizer concentration, incubation times, and light parameters. The review identifies the key limitations, such as RB’s poor biofilm penetration and high dark toxicity at elevated concentrations, which hinder its clinical applicability. The combination of RB with potassium iodide enhances its antifungal efficacy, suggesting that further optimization could improve its clinical potential. Overall, while Rose Bengal-mediated aPDT holds promise as a novel antifungal treatment, further research is needed to standardize protocols, enhance delivery systems, and validate its efficacy in vivo and clinical settings. Full article
(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)
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17 pages, 4988 KiB  
Article
Porous Carbon Derived from Pumpkin Tissue as an Efficient Bioanode Toward Wastewater Treatment in Microbial Fuel Cells
by Jiaxin Liu, Xue Yan, Qiang Ding, Jiwu Xiang, Zuna Wei, Qian Yang, Kangwei Xie, Bo Cheng and Xiaoying Xie
Sustainability 2025, 17(11), 4758; https://doi.org/10.3390/su17114758 - 22 May 2025
Viewed by 350
Abstract
A novel three-dimensional porous biocarbon electrode with exceptional biocompatibility was synthesized via a facile approach using pumpkin as the precursor. The obtained pumpkin-derived biocarbon features a highly porous architecture and serves as an efficient biocarbon electrode (denoted as PBE) in a microbial fuel [...] Read more.
A novel three-dimensional porous biocarbon electrode with exceptional biocompatibility was synthesized via a facile approach using pumpkin as the precursor. The obtained pumpkin-derived biocarbon features a highly porous architecture and serves as an efficient biocarbon electrode (denoted as PBE) in a microbial fuel cell (MFC). This PBE could form robust biofilms to facilitate the adhesion of electroactive bacteria. When used in the treatment of real wastewater, the assembled PBE-MFC achieves a remarkable power density of 231 mW/m2, much higher than the control (carbon brush—MFC, 164 mW/m2) under the identical conditions. This result may be attributed to the upregulation of flagellar assembly pathways and bacterial secretion systems in the electroactive bacteria (e.g., Hydrogenophaga, Desulfovibrio, Thiobacillus, Rhodanobacter) at the anode of the PBE-MFC. The increased abundance of nitrifying bacteria (e.g., Hyphomicrobium, Sulfurimonas, Aequorivita) and organic matter-degrading bacteria (e.g., Lysobacter) in the PBE-MFC also contributed to its exceptional wastewater treatment efficiency. With its outstanding biocompatibility, cost-effectiveness, environmental sustainability, and ease of fabrication, the PBE-MFC displays great potential for application in the field of high-performance and economic wastewater treatment. Full article
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