Coagulation factor replacement therapy for the X-linked bleeding disorder Haemophilia, characterized by a deficiency of coagulation protein factor VIII (FVIII), is severely complicated by antibody (inhibitors) formation. The development of FVIII inhibitors drastically alters the quality of life of the patients and is associated with a tremendous increase in morbidity as well as treatment costs. The ultimate goal of inhibitor control is antibody elimination. Immune tolerance induction (ITI) is the only clinically established approach for developing antigen-specific tolerance to FVIII. This work aims to establish a novel cost-effective strategy to produce FVIII molecules in fusion with cholera toxin B (CTB) subunit at the N terminus using the Bacillus subtilis expression system for oral tolerance, as the current clinical immune tolerance protocols are expensive. Regions of B-Domain Deleted (BDD)-FVIII that have potential epitopes were identified by employing Bepipred linear epitope prediction; 2 or more epitopes in each domain were combined and cDNA encoding these regions were fused with CTB and cloned in the Bacillus subtilis expression vector pHT43 and expression analysis was carried out. The expressed CTB-fused FVIII epitope domains showed strong binding affinity towards the CTB-receptor GM1 ganglioside. To conclude, Bacillus subtilis expressing FVIII molecules might be a promising candidate for exploring for the induction of oral immune tolerance.
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http://dx.doi.org/10.1007/s12223-024-01166-z | DOI Listing |
During growth, differentiates into subpopulations of motile individuals and non-motile chains, associated with dispersal and biofilm formation respectively. The two cell types are dictated by the activity of the alternative sigma factor SigD encoded as the penultimate gene of the 27 kb long flagellar operon. The frequency of SigD-ON motile cells is increased by the heteromeric transcription factor SwrA•DegU that activates the promoter.
View Article and Find Full Text PDFACS Biomater Sci Eng
January 2025
Faculty of Biotechnology and Food Engineering, Technion─Israel Institute of Technology, Haifa 3200003, Israel.
The skin, our first line of defense against external threats, combines a physical barrier and a rich microbial community. Disruptions of this community, for example, due to infectious injury, have been linked to a decrease in bacteria diversity and to mild to severe pathological conditions. Although some progress has been made in the field, possibilities/procedures for restoring the skin microbiome are still far from ideal.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Biology, Indiana University, 1001 E 3rd Street, Bloomington, IN 47405, USA.
Genome organization is important for DNA replication, gene expression, and chromosome segregation. In bacteria, two large families of proteins, nucleoid-associated proteins (NAPs) and SMC complexes, play important roles in organizing the genome. NAPs are highly abundant DNA-binding proteins that can bend, wrap, bridge, and compact DNA, while SMC complexes load onto the chromosome, translocate on the DNA, and extrude DNA loops.
View Article and Find Full Text PDFFood Chem Toxicol
January 2025
Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, 40201, Taiwan; Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, 40201, Taiwan. Electronic address:
Since red beans have poor textural properties, fermentation is commonly used to help produce better pulse products. To obtain BLR-E50, red beans are fermented using a co-culture of Bacillus subtilis and Lactobacillus bulgaricus, followed by extraction with 50% ethanol. The present data demonstrate that BLR-E50 did not exhibit mutagenicity, genotoxicity, or subacute oral toxicity.
View Article and Find Full Text PDFMeat Sci
January 2025
College of Food Science and Engineering, Shandong Agricultural University, Taian 271018, Shandong, PR China. Electronic address:
This study aimed to investigate the effects of dietary Bacillus subtilis (B. subtilis) supplementation in pigs on the meat color and oxidative stability of the meat under high‑oxygen packaging. The results showed B.
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