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Search Results (4,355)

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Keywords = in vivo infection

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14 pages, 1215 KiB  
Article
Daptomycin-Loaded Nano-Drug Delivery System Based on Biomimetic Cell Membrane Coating Technology: Preparation, Characterization, and Evaluation
by Yuqin Zhou, Shihan Du, Kailun He, Beilei Zhou, Zixuan Chen, Cheng Zheng, Minghao Zhou, Jue Li, Yue Chen, Hu Zhang, Hong Yuan, Yinghong Li, Yan Chen and Fuqiang Hu
Pharmaceuticals 2025, 18(8), 1169; https://doi.org/10.3390/ph18081169 - 6 Aug 2025
Abstract
Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short [...] Read more.
Background/Objective: Staphylococcus aureus (S. aureus) is a clinically significant pathogenic bacterium. Daptomycin (DAP) is a cyclic lipopeptide antibiotic used to treat infections caused by multidrug-resistant Gram-positive bacteria, including S. aureus. However, DAP currently faces clinical limitations due to its short half-life, toxic side effects, and increasingly severe drug resistance issues. This study aimed to develop a biomimetic nano-drug delivery system to enhance targeting ability, prolong blood circulation, and mitigate resistance of DAP. Methods: DAP-loaded chitosan nanocomposite particles (DAP-CS) were prepared by electrostatic self-assembly. Macrophage membrane vesicles (MM) were prepared by fusion of M1-type macrophage membranes with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). A biomimetic nano-drug delivery system (DAP-CS@MM) was constructed by the coextrusion process of DAP-CS and MM. Key physicochemical parameters, including particle diameter, zeta potential, encapsulation efficiency, and membrane protein retention, were systematically characterized. In vitro immune escape studies and in vivo zebrafish infection models were employed to assess the ability of immune escape and antibacterial performance, respectively. Results: The particle size of DAP-CS@MM was 110.9 ± 13.72 nm, with zeta potential +11.90 ± 1.90 mV, and encapsulation efficiency 70.43 ± 1.29%. DAP-CS@MM retained macrophage membrane proteins, including functional TLR2 receptors. In vitro immune escape assays, DAP-CS@MM demonstrated significantly enhanced immune escape compared with DAP-CS (p < 0.05). In the zebrafish infection model, DAP-CS@MM showed superior antibacterial efficacy over both DAP and DAP-CS (p < 0.05). Conclusions: The DAP-CS@MM biomimetic nano-drug delivery system exhibits excellent immune evasion and antibacterial performance, offering a novel strategy to overcome the clinical limitations of DAP. Full article
(This article belongs to the Section Pharmaceutical Technology)
24 pages, 10760 KiB  
Article
Pseudomonas Phage Banzai: Genomic and Functional Analysis of Novel Pbunavirus with Lytic Activity Against Pseudomonas aeruginosa
by Andrei V. Chaplin, Nina N. Sykilinda, George A. Skvortsov, Konstantin S. Troshin, Anna A. Vasilyeva, Sofia A. Shuraleva, Artem A. Malkov, Vladislav S. Simonov, Boris A. Efimov, Lyudmila I. Kafarskaia, Konstantin A. Miroshnikov, Anna A. Kuznetsova and Peter V. Evseev
Viruses 2025, 17(8), 1088; https://doi.org/10.3390/v17081088 - 6 Aug 2025
Abstract
Antibiotic-resistant Pseudomonas aeruginosa presents a critical global health challenge, particularly in hospital-acquired infections. Bacteriophages offer a promising therapeutic avenue due to their ability to target and lyse resistant strains. This study characterizes Pseudomonas phage Banzai, a newly isolated Pbunavirus (family Lindbergviridae) with [...] Read more.
Antibiotic-resistant Pseudomonas aeruginosa presents a critical global health challenge, particularly in hospital-acquired infections. Bacteriophages offer a promising therapeutic avenue due to their ability to target and lyse resistant strains. This study characterizes Pseudomonas phage Banzai, a newly isolated Pbunavirus (family Lindbergviridae) with lytic activity against multiple P. aeruginosa isolates, including multidrug-resistant strains. Genomic analysis revealed a 66,189 bp genome, lacking antibiotic resistance or virulence factors, and suggested a headful packaging mechanism and the presence of a bidirectional component in the replication. In vivo experiments using Galleria mellonella showed therapeutic potential, significantly improving larval survival (87% at 24 h). Host range analysis revealed activity against 13 of 30 P. aeruginosa isolates, including members of O1, O3, O5 and O6 in silico predicted serogroups. Phylogenomic analyses place phage Banzai within the genus Pbunavirus, sharing 94.8% intergenomic similarity with its closest relatives, supporting its classification as a novel species. These findings highlight phage Banzai as a potential candidate for phage therapy, demonstrating genomic stability, a strictly lytic lifestyle, and in vivo efficacy. Full article
(This article belongs to the Section Bacterial Viruses)
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16 pages, 1674 KiB  
Article
Enhanced Anticancer Activity of Atractylodin-Loaded Poly(lactic-co-glycolic Acid) Nanoparticles Against Cholangiocarcinoma
by Tullayakorn Plengsuriyakarn, Luxsana Panrit and Kesara Na-Bangchang
Polymers 2025, 17(15), 2151; https://doi.org/10.3390/polym17152151 - 6 Aug 2025
Abstract
Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea [...] Read more.
Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE2, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article
(This article belongs to the Section Polymer Applications)
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41 pages, 3389 KiB  
Review
Fully Green Particles Loaded with Essential Oils as Phytobiotics: A Review on Preparation and Application in Animal Feed
by Maria Sokol, Ivan Gulayev, Margarita Chirkina, Maksim Klimenko, Olga Kamaeva, Nikita Yabbarov, Mariia Mollaeva and Elena Nikolskaya
Antibiotics 2025, 14(8), 803; https://doi.org/10.3390/antibiotics14080803 - 6 Aug 2025
Abstract
The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the [...] Read more.
The modern livestock industry incorporates widely used antibiotic growth promoters into animal feed at sub-therapeutic levels to enhance growth performance and feed efficiency. However, this practice contributes to the emergence of antibiotic-resistant pathogens in livestock, which may be transmitted to humans through the food chain, thereby diminishing the efficacy of antibiotics in treating bacterial infections. Current research explores the potential of essential oils from derived medicinal plants as alternative phytobiotics. This review examines modern encapsulation strategies that incorporate essential oils into natural-origin matrices to improve their stability and control their release both in vitro and in vivo. We discuss a range of encapsulation approaches utilizing polysaccharides, gums, proteins, and lipid-based carriers. This review highlights the increasing demand for antibiotic alternatives in animal nutrition driven by regulatory restrictions, and the potential benefits of essential oils in enhancing feed palatability and stabilizing the intestinal microbiome in monogastric animals and ruminants. Additionally, we address the economic viability and encapsulation efficiency of different matrix formulations. Full article
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17 pages, 1027 KiB  
Review
Chimeric Antigen Receptor Immunotherapy for Infectious Diseases: Current Advances and Future Perspectives
by Maria Kourti, Paschalis Evangelidis, Emmanuel Roilides and Elias Iosifidis
Pathogens 2025, 14(8), 774; https://doi.org/10.3390/pathogens14080774 - 5 Aug 2025
Abstract
Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and [...] Read more.
Chimeric antigen receptor (CAR)-T immunotherapy has revolutionized the management of patients with relapsed/refractory B-cell hematological malignancies. There is emerging evidence that CAR-engineered cells—not only T cells, but also natural killers and macrophages—might have a crucial role in the treatment of autoimmune disorders and solid tumors. Moreover, given the burden of chronic infectious diseases, the mortality and morbidity of infections in immunocompromised individuals, and the development of multidrug-resistant pathogens, including bacteria, fungi, and mycobacteria, a need for novel and personalized therapeutics in this field is emerging. To this end, the development of CAR cells for the management of chronic infections has been reported. In this literature review, we summarize the ongoing clinical and pre-clinical data about CAR cell products in the field of infectious diseases. Currently, clinical studies on CAR immunotherapy for infections mainly concern human immunodeficiency virus infection treatment, and data regarding other infections largely originate from preclinical in vitro and in vivo models. In the era of personalized medicine, effective and safe therapies for the management of chronic infections and infectious complications in immunocompromised patients are crucial. Full article
(This article belongs to the Special Issue Bacterial Resistance and Novel Therapeutic Approaches)
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21 pages, 632 KiB  
Review
DNA Methylation in Bladder Cancer: Diagnostic and Therapeutic Perspectives—A Narrative Review
by Dragoş Puia, Marius Ivănuță and Cătălin Pricop
Int. J. Mol. Sci. 2025, 26(15), 7507; https://doi.org/10.3390/ijms26157507 - 3 Aug 2025
Viewed by 220
Abstract
Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current [...] Read more.
Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current evidence on the role of DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and the hypermethylation of key tumour suppressor genes, including A2BP1, NPTX2, SOX11, PENK, NKX6-2, DBC1, MYO3A, and CA10, in bladder cancer. It also evaluates the therapeutic application of DNA-demethylating agents such as 5-azacytidine and highlights the impact of chronic inflammation on epigenetic regulation. Promoter hypermethylation of tumour suppressor genes leads to transcriptional silencing and unchecked cell proliferation. Urine-based DNA methylation assays provide a sensitive and specific method for non-invasive early detection, with single-target approaches offering high diagnostic precision. Animal models are increasingly employed to validate these findings, allowing the study of methylation dynamics and gene–environment interactions in vivo. DNA methylation represents a key epigenetic mechanism in bladder cancer, with significant diagnostic, prognostic, and therapeutic implications. Integration of human and experimental data supports the use of methylation-based biomarkers for early detection and targeted treatment, paving the way for personalized approaches in bladder cancer management. Full article
(This article belongs to the Section Molecular Oncology)
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12 pages, 579 KiB  
Article
In Vivo Safety and Efficacy of Thiosemicarbazones in Experimental Mice Infected with Toxoplasma gondii Oocysts
by Manuela Semeraro, Ghalia Boubaker, Mirco Scaccaglia, Dennis Imhof, Maria Cristina Ferreira de Sousa, Kai Pascal Alexander Hänggeli, Anitha Löwe, Marco Genchi, Laura Helen Kramer, Alice Vismarra, Giorgio Pelosi, Franco Bisceglie, Luis Miguel Ortega-Mora, Joachim Müller and Andrew Hemphill
Biomedicines 2025, 13(8), 1879; https://doi.org/10.3390/biomedicines13081879 - 1 Aug 2025
Viewed by 157
Abstract
Background: Toxoplasma gondii is a globally widespread parasite responsible for toxoplasmosis, a zoonotic disease with significant impact on both human and animal health. The current lack of safe and effective treatments underscores the need for new drugs. Earlier, thiosemicarbazones (TSCs) and their [...] Read more.
Background: Toxoplasma gondii is a globally widespread parasite responsible for toxoplasmosis, a zoonotic disease with significant impact on both human and animal health. The current lack of safe and effective treatments underscores the need for new drugs. Earlier, thiosemicarbazones (TSCs) and their metal complexes have shown promising activities against T. gondii. This study evaluated a gold (III) complex C3 and its TSC ligand C4 for safety in host immune cells and zebrafish embryos, followed by efficacy assessment in a murine model for chronic toxoplasmosis. Methods: The effects on viability and proliferation of murine splenocytes were determined using Alamar Blue assay and BrdU ELISA, and potential effects of the drugs on zebrafish (Danio rerio) embryos were detected through daily light microscopical inspection within the first 96 h of embryo development. The parasite burden in treated versus non-treated mice was measured by quantitative real-time PCR in the brain, eyes and the heart. Results: Neither compound showed immunosuppressive effects on the host immune cells but displayed dose-dependent toxicity on early zebrafish embryo development, suggesting that these compounds should not be applied in pregnant animals. In the murine model of chronic toxoplasmosis, C4 treatment significantly reduced the parasite load in the heart but not in the brain or eyes, while C3 did not have any impact on the parasite load. Conclusions: These results highlight the potential of C4 for further exploration but also the limitations of current approaches in effectively reducing parasite burden in vivo. Full article
(This article belongs to the Section Microbiology in Human Health and Disease)
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8 pages, 912 KiB  
Article
Methenamine as an Alternative Treatment of Neisseria gonorrhoeae Urethritis? An In Vitro and In Vivo Study in Galleria mellonella
by Izumo Kanesaka, Saïd Abdellati, Sheeba Santhini Manoharan-Basil and Chris Kenyon
Venereology 2025, 4(3), 13; https://doi.org/10.3390/venereology4030013 - 1 Aug 2025
Viewed by 101
Abstract
Background: There is an urgent need for novel treatment options for Neisseria gonorrhoeae. Methenamine is an interesting urinary antiseptic with a very low propensity to induce antimicrobial resistance. Methods: We assessed the MICs of methenamine-hippurate for 18 N. gonorrhoeae isolates. We then [...] Read more.
Background: There is an urgent need for novel treatment options for Neisseria gonorrhoeae. Methenamine is an interesting urinary antiseptic with a very low propensity to induce antimicrobial resistance. Methods: We assessed the MICs of methenamine-hippurate for 18 N. gonorrhoeae isolates. We then assessed the in vivo efficacy of methenamine-hippurate against N. gonorrhoeae using the Galleria mellonella infection model. Results: We found that all the gonococcal isolates had a methenamine-hippurate MIC of 300 mg/L. This MIC was not higher in isolates with higher ceftriaxone MICs. No toxicity of methenamine at the doses tested was found, and doses as low as 200 mg/kg were effective in the G. mellonella model. Conclusions: Further studies in mice and humans are required to assess if methenamine-hippurate could be used to treat gonococcal urethritis alone or in combination with other agents such as ceftriaxone. Full article
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25 pages, 9193 KiB  
Article
Antibiotic-Loaded Bioglass 45S5 for the Treatment and Prevention of Staphylococcus aureus Infections in Orthopaedic Surgery: A Novel Strategy Against Antimicrobial Resistance
by Humera Sarwar, Richard A. Martin, Heather M. Coleman, Aaron Courtenay and Deborah Lowry
Pathogens 2025, 14(8), 760; https://doi.org/10.3390/pathogens14080760 - 1 Aug 2025
Viewed by 270
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Antimicrobial Resistance in the Post-COVID Era: A Silent Pandemic)
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15 pages, 286 KiB  
Review
Strategies for Maximising Lung Utilisation in Donors After Brain and Cardiac Death: A Narrative Review
by Carola Pergolizzi, Chiara Lazzeri, Daniele Marianello, Cesare Biuzzi, Casagli Irene, Antonella Puddu, Elena Bargagli, David Bennett, Chiara Catelli, Luca Luzzi, Francesca Montagnani, Francisco Del Rio Gallegos, Sabino Scolletta, Adriano Peris and Federico Franchi
J. Clin. Med. 2025, 14(15), 5380; https://doi.org/10.3390/jcm14155380 - 30 Jul 2025
Viewed by 273
Abstract
Lung transplantation remains the standard of care for end-stage lung disease, yet a persistent gap exists between donor lung availability and growing clinical demand. Expanding the donor pool and optimising donor lung management are therefore critical priorities. However, no universally accepted management protocols [...] Read more.
Lung transplantation remains the standard of care for end-stage lung disease, yet a persistent gap exists between donor lung availability and growing clinical demand. Expanding the donor pool and optimising donor lung management are therefore critical priorities. However, no universally accepted management protocols are currently in place. This narrative review examines evidence-based strategies to improve lung utilisation across three donor categories: donors after brain death (DBD), controlled donors after circulatory death (cDCD), and uncontrolled donors after circulatory death (uDCD). A systematic literature search was conducted to identify interventions targeting lung preservation and function, including protective ventilation, recruitment manoeuvres, fluid and hormonal management, and ex vivo lung perfusion (EVLP). Distinct pathophysiological mechanisms—sympathetic storm and systemic inflammation in DBD, ischaemia–reperfusion injury in cDCD, and prolonged warm ischaemia in uDCD—necessitate tailored approaches to lung preservation. In DBD donors, early application of protective ventilation, bronchoscopy, and infection surveillance is essential. cDCD donors benefit from optimised pre- and post-withdrawal management to mitigate lung injury. uDCD donor lungs, uniquely vulnerable to ischaemia, require meticulous post-mortem evaluation and preservation using EVLP. Implementing structured, evidence-based lung management strategies can significantly enhance donor lung utilisation and expand the transplantable organ pool. The integration of such practices into clinical protocols is vital to addressing the global shortage of suitable lungs for transplantation. Full article
(This article belongs to the Section Respiratory Medicine)
22 pages, 2147 KiB  
Article
Streamlining Bacillus Strain Selection Against Listeria monocytogenes Using a Fluorescence-Based Infection Assay Integrated into a Multi-Tiered Validation Pipeline
by Blanca Lorente-Torres, Pablo Castañera, Helena Á. Ferrero, Sergio Fernández-Martínez, Suleiman Adejoh Ocholi, Jesús Llano-Verdeja, Farzaneh Javadimarand, Yaiza Carnicero-Mayo, Amanda Herrero-González, Alba Puente-Sanz, Irene Sainz Machín, Isabel Karola Voigt, Silvia Guerrero Villanueva, Álvaro López García, Eva Martín Gómez, James C. Ogbonna, José M. Gonzalo-Orden, Jesús F. Aparicio, Luis M. Mateos, Álvaro Mourenza and Michal Letekadd Show full author list remove Hide full author list
Antibiotics 2025, 14(8), 765; https://doi.org/10.3390/antibiotics14080765 - 29 Jul 2025
Viewed by 275
Abstract
Background/Objectives: Listeria monocytogenes is a foodborne pathogen of major public health concern due to its ability to invade host cells and cause severe illness. This study aimed to develop and validate a multi-tiered screening pipeline to identify Bacillus strains with probiotic potential [...] Read more.
Background/Objectives: Listeria monocytogenes is a foodborne pathogen of major public health concern due to its ability to invade host cells and cause severe illness. This study aimed to develop and validate a multi-tiered screening pipeline to identify Bacillus strains with probiotic potential against L. monocytogenes. Methods: A total of 26 Bacillus isolates were screened for antimicrobial activity, gastrointestinal resilience, and host cell adhesion. A fluorescence-based infection assay using mCherry-expressing HCT 116 cells was used to assess cytoprotection against L. monocytogenes NCTC 7973. Eight strains significantly improved host cell viability and were validated by quantification of intracellular CFU. Two top candidates were tested in a murine model of listeriosis. The genome of the lead strain was sequenced to evaluate safety and biosynthetic potential. Results: B. subtilis CECT 8266 completely inhibited intracellular replication of L. monocytogenes in HCT 116 cells, reducing bacterial recovery to undetectable levels. In vivo, it decreased splenic bacterial burden by approximately 6-fold. Genomic analysis revealed eight bacteriocin biosynthetic clusters and silent antibiotic resistance genes within predicted genomic islands, as determined by CARD and Alien Hunter analysis. The strain also demonstrated bile and acid tolerance, as well as strong adhesion to epithelial cells. Conclusions: The proposed pipeline enables efficient identification of probiotic Bacillus strains with intracellular protective activity. B. subtilis CECT 8266 is a promising candidate for translational applications in food safety or health due to its efficacy, resilience, and safety profile. Full article
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21 pages, 2233 KiB  
Article
In the Absence of Type-1 IFN, HSV-1 LAT Increases γ34.5 Expression and Enhances Mortality in Infected Mice
by Jay J. Oh, Ujjaldeep Jaggi, Deepak Arya, Shaohui Wang and Homayon Ghiasi
Viruses 2025, 17(8), 1061; https://doi.org/10.3390/v17081061 - 29 Jul 2025
Viewed by 359
Abstract
Type-I Interferon (IFN) is essential for antiviral immunity in both mice and humans; thus, we investigated whether LAT affects HSV-1 infectivity in the absence of IFN by infecting IFNαβR−/− and wild-type control mice with HSV-1 McKrae (LAT-plus) and dLAT2903 (LAT-minus) viruses. IFNαβR [...] Read more.
Type-I Interferon (IFN) is essential for antiviral immunity in both mice and humans; thus, we investigated whether LAT affects HSV-1 infectivity in the absence of IFN by infecting IFNαβR−/− and wild-type control mice with HSV-1 McKrae (LAT-plus) and dLAT2903 (LAT-minus) viruses. IFNαβR−/− mice survived ocular infection with the LAT-plus virus, while no infected mice survived infection with the LAT-minus virus. Increased death in infected mice correlated with a higher expression in the neurovirulence γ34.5 gene but not with gB expression. To determine the region of LAT that contributed to higher mortality, IFNαβR−/− mice were infected with recombinant viruses expressing the first 1.5 kb or the first 811bp region of 1.5 kb LAT. Similar to LAT-plus infected mice, IFNαβR−/− mice infected with LAT1.5kb were protected from death, while infection with the LAT811bp virus was similar to that of LAT-minus, suggesting that increased pathogenicity in the absence of LAT depends on the second half of 1.5 kb LAT. To confirm the in vivo upregulation of γ34.5 expression in the absence of LAT, rabbit skin and Neuro2A cells were infected with LAT-plus, LAT-minus, LAT1.5kb, or LAT811bp viruses. γ34.5 expression was significantly higher in LAT-minus- and LAT811bp-infected rabbit skin cells and Neuro2A cells than in LAT-plus- and LAT1.5kb-infected cells, suggesting that sequences after the 811bp of LAT contribute to γ34.5 upregulation. However, except for γ34.5 expression, ICP0, ICP4, and gB expression were not affected by the absence of LAT or truncated forms of LAT. To confirm that higher γ34.5 expression contributes to higher mortality in the absence of LAT, we infected IFNαβR−/− mice with a recombinant virus lacking LAT and γ34.5 expression, and, in contrast to LAT-minus, all infected mice survived. Our results suggest that LAT controls γ34.5 expression and that higher γ34.5 expression and mortality in infected mice are associated with the second half of 1.5 kb LAT. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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20 pages, 2840 KiB  
Article
Functional Analysis of BmHemolin in the Immune Defense of Silkworms
by Long He, Lijing Liu, Huawei Liu, Xin Tang, Yide Meng, Hui Xie, Lin Zhu, Qingyou Xia and Ping Zhao
Insects 2025, 16(8), 778; https://doi.org/10.3390/insects16080778 - 29 Jul 2025
Viewed by 442
Abstract
Hemolin has been identified as a crucial immune gene in insect immune defense. The silkworm is susceptible to infections by pathogenic microorganisms when reared on artificial diets. In this study, through comparative analysis of the expression patterns of BmHemolin in silkworms fed on [...] Read more.
Hemolin has been identified as a crucial immune gene in insect immune defense. The silkworm is susceptible to infections by pathogenic microorganisms when reared on artificial diets. In this study, through comparative analysis of the expression patterns of BmHemolin in silkworms fed on mulberry leaves and artificial diets, we found that the expression of BmHemolin was significantly upregulated in silkworms reared on artificial diets, and this upregulation was highly likely induced by pathogenic microorganisms. Further interaction analysis revealed that BmHemolin could bind to pathogenic microorganisms and form aggregates. Meanwhile, BmHemolin enhanced the melanization and aggregation of hemocytes. Subsequent in vitro antibacterial experiments showed that BmHemolin had the ability to inhibit the growth of Escherichia coli. In vivo clearance experiments demonstrated that BmHemolin facilitated the clearance of pathogens in the body. Moreover, CRISPR/Cas9-mediated knockout of the BmHemolin gene led to the downregulation of antimicrobial peptides and phagocytosis-related factors, while an excess of BmHemolin could enhance the expression of these genes, thereby improving the silkworm’s immune resistance to Enterococcus mundtii and increasing survival rates. In summary, our research demonstrates that BmHemolin played a pivotal role in both humoral and cellular immunity in the silkworm, thereby defending against pathogen invasion. Full article
(This article belongs to the Section Insect Molecular Biology and Genomics)
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14 pages, 1450 KiB  
Article
Characterization and Complete Genomic Analysis of a Novel Bacteriophage BUCT775 for Acinetobacter baumannii and Its Elimination Efficiency in the Environment
by Yuxuan Liu, Yunfei Huang, Dongxiang Zhu, Lefei Zhang, Jianwei Zhang, Yigang Tong and Mengzhe Li
Int. J. Mol. Sci. 2025, 26(15), 7279; https://doi.org/10.3390/ijms26157279 - 28 Jul 2025
Viewed by 211
Abstract
Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen responsible for a range of severe infections and nosocomial outbreaks. Phage-based therapy and biocontrol represent effective strategies to combat the prevalence of A. baumannii. This study reports a novel phage, BUCT775, capable [...] Read more.
Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen responsible for a range of severe infections and nosocomial outbreaks. Phage-based therapy and biocontrol represent effective strategies to combat the prevalence of A. baumannii. This study reports a novel phage, BUCT775, capable of specifically lysing A. baumannii, and investigates its physiological properties, genomic characteristics, in vivo therapeutic efficacy, and environmental disinfection performance. Phage BUCT775 is a podovirus that forms clear, well-defined plaques with an average diameter of 2.5 ± 0.52 mm. It exhibits a broad range of temperature stability (4–55 °C) and pH stability (pH 3–12). The optimal multiplicity of infection (MOI) for phage BUCT775 is 0.01. At an MOI of 0.01, it demonstrates a latent period of approximately 10 min and exhibits a high burst size. Genomic sequencing and bioinformatics analysis revealed that phage BUCT775 belongs to the order Caudoviricetes and the family Autographiviridae. Its genome has a G + C content of 39.3% and is not known to contain virulence genes or antibiotic resistance genes. Phage BUCT775 exhibited significant therapeutic effects on A. baumannii-infected G. mellonella larvae, increasing the 120 h survival rate of the larvae by 20%. Additionally, phage BUCT775 efficiently eliminated A. baumannii in the environment, with an average clearance rate exceeding 98% within 3 h. These studies suggest that phage BUCT775 holds significant potential for application in phage therapy and environmental disinfection. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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9 pages, 340 KiB  
Communication
Sciatic Integrity Is Necessary for Fast and Efficient Scrapie Infection After Footpad Injection
by Franco Cardone, Flavia Porreca, Marco Sbriccoli, Anna Poleggi, Anna Ladogana, Mei Lu, Maurizio Pocchiari and Luigi Di Giamberardino
Int. J. Mol. Sci. 2025, 26(15), 7273; https://doi.org/10.3390/ijms26157273 - 28 Jul 2025
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Abstract
The agents of prion diseases have the capacity to efficiently infect susceptible hosts by peripheral routes and to project to clinical target areas of the central nervous system (CNS) via peripheral nerves. Understanding the process of prion spread from the site of infection [...] Read more.
The agents of prion diseases have the capacity to efficiently infect susceptible hosts by peripheral routes and to project to clinical target areas of the central nervous system (CNS) via peripheral nerves. Understanding the process of prion spread from the site of infection to the CNS may allow us to identify novel therapeutic strategies. To investigate the mechanism involved in the intranerval transit of 263K scrapie prions in golden Syrian hamsters (GSHs), we transected the sciatic nerve at increasing times post-footpad injection and recorded the incubation periods as estimates of the efficiency of infection. We calculated that intranerval transit of this strain of scrapie is at least 10 times faster than previously reported and may reach 50 mm/day, similar to other neurotropic viruses. By in vivo exposure/injection of sciatic nerves to 263K infectivity, we have also shown that prion entry likely occurs via nerve terminals rather than by direct contact with the sciatic nerve. Application of this experimental approach in other forms of prion diseases could allow verification of the timing of neuroinvasion, a relevant parameter for the definition of therapeutic interventions. Full article
(This article belongs to the Section Molecular Neurobiology)
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