A subunit vaccine against pneumonia: targeting Streptococcus pneumoniae and Klebsiella pneumoniae.

Community-acquired pneumonia is primarily caused by Streptococcus pneumoniae and Klebsiella pneumoniae, two pathogens that have high morbidity and mortality rates. This is largely due to bacterial resistance development against current antibiotics and the lack of effective vaccines. The objective of this work was to develop an immunogenic multi-epitope subunit vaccine capable of eliciting a robust immune response against S. pneumoniae and K. pneumoniae. The targeted proteins were the pneumococcal surface proteins (PspA and PspC) and choline-binding protein (CbpA) of S. pneumoniae and the outer membrane proteins (OmpA and OmpW) of K. pneumoniae. Different computational approaches and various immune filters were employed for designing a vaccine. The immunogenicity and safety of the vaccine were evaluated by utilizing many physicochemical and antigenic profiles. To improve structural stability, disulfide engineering was applied to a portion of the vaccine structure with high mobility. Molecular docking was performed to examine the binding affinities and biological interactions at the atomic level between the vaccine and Toll-like receptors (TLR2 and 4). Further, the dynamic stabilities of the vaccine and TLRs complexes were investigated by molecular dynamics simulations. While the immune response induction capability of the vaccine was assessed by the immune simulation study. Vaccine translation and expression efficiency was determined through an in silico cloning experiment utilizing the pET28a(+) plasmid vector. The obtained results revealed that the designed vaccine is structurally stable and able to generate an effective immune response to combat pneumococcal infection. Supplementary Information: The online version contains supplementary material available at 10.1007/s13721-023-00416-3.

Genomic analysis and in vivo efficacy of Pediococcus acidilactici as a potential probiotic to prevent hyperglycemia, hypercholesterolemia and gastrointestinal infections.

Lactic acid bacteria are the well acknowledged probiotics that can cure a variety of diseases. In this study, we observed the in vivo potentials of Pediococcus to treat hyperglycemia, hypercholesterolemia and gastrointestinal infections. A total of 77 Lactobacillus were isolated from the milk of 10 cows and 10 goats, four of those strains inhibited both carbohydrates-hydrolyzing enzymes, α-glucosidase, and α-amylase. They all showed antagonistic effects on pathogenic E. coli and S. Typhimurium which were confirmed by performing pathogen challenge test and visualizing on Electron microscopy. 16S rRNA gene sequence identified that all four strains belong to Pediococcus genus which were further distinguished as Pediococcus acidilactici by pheS gene sequence. Whole genome sequence analysis revealed their non-pathogenic properties for human and the presence of probiotic genes responsible for stress resistance, immunomodulation, adhesion, metal and drug resistance. In vivo trial with diabetes-induced mice ascertained that all Pediococcus acidilactici had significant potentials to reduce elevated glucose and low-density lipoprotein level in blood. Interestingly, two out of four strains were significantly more effective (p < 0.0001 each) than metformin in reducing the blood glucose level. This in vivo study demonstrated that Pediococcus acidilactici might be a promising probiotic to prevent hyperglycemia, hypercholesterolemia and gastrointestinal infections.

Immune epitopes identification and designing of a multi-epitope vaccine against bovine leukemia virus: a molecular dynamics and immune simulation approaches.

BACKGROUND: Bovine leukemia virus (BLV) is an oncogenic delta-retrovirus causing bovine leucosis. Studies on BLV have shown the association with human breast cancer. However, the exact molecular mechanism is neither known nor their appropriate preventative measure to halt the disease initiation and progression. In this study, we designed a multi-epitope vaccine against BLV using a computational analyses. METHODS: Following a rigorous assessment, the vaccine was constructed using the T-cell epitopes from each BLV-derived protein with suitable adjuvant and linkers. Both physicochemistry and immunogenic potency as well as the safeness of the vaccine candidate were assessed. Population coverage was done to evaluate the vaccine probable efficiency in eliciting the immune response worldwide. After homology modeling, the three-dimensional structure was refined and validated to determine the quality of the designed vaccine. The vaccine protein was then subjected to molecular docking with Toll-like receptor 3 (TLR3) to evaluate the binding efficiency followed by dynamic simulation for stable interaction. RESULTS: Our vaccine construct has the potential immune response and good physicochemical properties. The vaccine is antigenic and immunogenic, and has no allergenic or toxic effect on the human body. This novel vaccine contains a significant interactions and binding affinity with the TLR3 receptor. CONCLUSIONS: The proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat BLV infections. However, experimental evaluations are essential to validate the exact safety and immunogenic profiling of this vaccine.

Assessment of antibacterial, anti-inflammatory, and cytotoxic effects of different extracts of Gynura procumbens leaf.

BACKGROUND: In Southeast Asia, Gynura procumbens has been utilized as a traditional medicinal herb for many diseases. The nontoxic effects of the leaves of G procumbens can be consumed safely for the treatment of many diseases, especially diabetes mellitus. OBJECTIVES: This study aimed to assess the antibacterial, anti-inflammatory, and cytotoxic effects of G procumbens leaves through different extracts. METHODS: Cold extraction was employed for G procumbens leaves. Disc diffusion, bovine serum albumin denaturation, brine shrimp lethality assays, and microscopic examination of tissues (ie, liver, kidney, and heart) were performed to measure antibacterial, anti-inflammatory, and cytotoxic activities, and histopathologic analysis, respectively. RESULTS: The distinct concentrations of aqueous, ethanol, and n-hexane extracts showed prominent antibacterial activity against four pathogenic bacterial strains (Chromobacterium sp, Staphylococcus aureus, Enterococcus faecium, and Escherichia coli 0157:H7:LT). The aqueous extract of G procumbens at a concentration of 200 µg/mL showed potential antibacterial activities against S aureus and E faecium, with mean (SD) zones of inhibition of 15 (1.0) mm and 10 (0.55) mm, respectively. At a concentration of 40 µg/mL, the aqueous extract of G procumbens exhibited significant (P < 0.01) anti-inflammatory activity compared with that of the other 2 extracts in the bovine serum albumin denaturation assay. The n-hexane extract showed moderate cytotoxic activity compared with that of vincristine sulfate. The median lethal concentration values of the aqueous, ethanol, and n-hexane extracts were 427.66, 218.56, and 114.51 µg/mL, respectively. The aqueous extract exhibited lower cytotoxicity than that exhibited by the ethanol and n-hexane extracts. The histopathologic analysis results showed that the aqueous extract of G procumbens had no harmful effects on the different organs of the experimental mice. CONCLUSIONS: The aqueous extract of G procumbens could be a potential source for treating various infectious and chronic diseases. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

Assessment of novel probiotic strains on growth, hematobiochemical parameters, and production costs of commercial broilers in Bangladesh.

BACKGROUND AND AIM: The use of antibiotic growth promoters (AGPs) in the poultry industry has raised concern because of their potential harm to human health. Emerging evidence suggests that probiotics are a safer substitute, although little research has explored this in Bangladesh. We recently isolated local bacterial strains with probiotic properties. We aimed to determine their impact on the growth, hematobiochemical parameters, and production costs of broiler chicks relative to that of a commercial probiotic (CP) and AGP. MATERIALS AND METHODS: Day-old male broiler chicks (Cobb 500, n=63) were divided equally into three experimental groups (three replicates per group and seven chicks per replicate). First group was fed a basal diet supplemented with the AGP, ciprofloxacin (CTL group), second group was fed a basal diet supplemented with the CP, Protexin® (CP group), and the third group was fed a basal diet supplemented with our isolated bacterial strains (study probiotic [SP] group) for 36 days. Body weight was recorded daily, and relative growth rate (RGR), feed conversion ratio (FCR), and organ weights and carcass yields were calculated at the study's end. Blood obtained on day 36 was used to determine the number of red blood cell (RBC) and white blood cells (WBCs), hemoglobin (Hb) concentration, packed cell volume, erythrocyte sedimentation rate, as well as levels of serum glucose, total and high-density lipoprotein (HDL) cholesterol, and triglycerides (TGs). Total production costs were estimated by summing the variable and fixed costs. RESULTS: Chicks in both the CP and SP groups experienced significant decreases in blood glucose levels and significant increases in BW, RGR, FCR, levels of RBC and WBC, Hb concentration, and packed cell volume compared with those in the CTL group (p<0.05 for all). Our data suggested a numerical reduction (p>0.05) in levels of total cholesterol, TGs, and HDL in the SP and CP groups when compared to the CTL group. In addition, both CP and SP treatments resulted in significant (p<0.05) gains in net profit compared with the treatment given to the CTL group. CONCLUSION: Administration of probiotics, either from a commercialized or local source, led to greater improvements in growth, hematological parameters, and net profits of broiler chicks when compared with that of an AGP. This suggests that they are suitable alternatives to the AGPs used in poultry feed and that our isolated strains, in particular, are an ideal option for farmers in Bangladesh.