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Multidrug-resistant wound infections are a global health threat and a leading cause of death, persisting despite available treatments due to antibiotic resistance, biofilms, and ineffective drug delivery systems. The aim of this study is to (i) formulate an innovative nano-drug delivery system (NDDS) based on a Carbopol nanoemulgel (NEG) co-loaded with neomycin-silver/zinc oxide nanocomposite (NC) that could fight clinical MDR and treat biofilm-forming wound pathogens through topical application, and (ii) assess its in vivo wound-healing potential. The silver/zinc oxide (Ag/ZnO) NC was synthesized by co-inoculating the metabolites of Aspergillus welwitschiae and Meyerozyma guilliermondii. The synthesized NC was then conjugated with neomycin and loaded into a Carbopol NEG for efficient topical delivery. The resulting Neo-Ag/ZnO NEG was characterized physicochemically (e.g., UV-visible [UV-Vis] spectrophotometry, field emission scanning electron microscopy, X-ray diffraction, and Fourier transform infrared [FTIR] spectroscopy), biologically (e.g., in vitro antimicrobial, antibiofilm, and hemolytic activities), and pharmacologically (e.g., drug content, ex vivo drug release behavior, and in vivo wound-healing potential). The physicochemical analysis confirmed the successful mycosynthesis of the Carbopol NEG-loaded Neo-Ag/ZnO NC. SEM depicted a crystalline polyhedral shape of the small NC (average particle size of 38 nm). FTIR studies showed a slight interaction with the drug and other bioactive moieties in the Carbopol NEG. The Neo content in the Carbopol NEG was as high as 98%, and a maximum release of 81% for Neo, Ag, and ZnO ions was noticed after 12 h. The NDDS appeared hemocompatible and displayed a minimal inhibition concentration of 0.002 µg/mL with the greatest antimicrobial potential against S. aureus (an inhibition zone of 46 mm) compared to other tested wound microbes (p < 0.05). Statistically significant wound-healing activity was found for NDDS (p = 0.0001) in comparison to the control at a concentration of 100 mg/mL. The results showed that this newly developed Carbopol NEG-loaded neo-Ag/ZnO NC appeared promising for controlling resistant skin infections and boosting wound regeneration.

The demand for vaccines, particularly those prepared from non-conventional sources, is rising due to the emergence of drug resistance around the globe. Probiotic-based vaccines are a wise example of such vaccines which represent new horizons in the field of vaccinology in providing an enhanced and diversified immune response. The justification for incorporating probiotics into vaccines lies in the fact that that they hold the capacity to regulate immune function directly or indirectly by influencing the gastrointestinal microbiota and related pathways. Several animal-model-based studies have also highlighted the efficacy of these vaccines. The aim of this review is to collect and summarize the trends in the recent scientific literature regarding the role of probiotics in vaccines and vaccinology, along with their impact on target populations. [ABSTRACT FROM AUTHOR]

The continued use of antibiotics is bringing extensive resistance in methicillinresistant Staphylococcus aureus (MRSA) of dairy animals and demands inclusion of non-antibiotic sources in treatment protocols. The current study aims to explore antibacterial potential of berberine (BR), artesunate (AR), and quercetin (QT) and extent of their resistance modulation capacity in combination with β-lactam antibiotics against MRSA. For this study, a total of 674 milk samples from dairy cows were collected for isolation of MRSA and thereafter phytochemicals (drugs) alone and in combination with β-lactams (penicillin, oxacillin, cefoxitin, ampicillin) were evaluated against MRSA. The synergy testing showed all synergistic effects except AR with penicillin which was additive effect. The synergism of antibiotics and phytochemicals was further confirmed by time-kill assay. The killing kinetics revealed a zero bacterial count at 16h of incubation in all combinations. Additionally, the killing synergy showed a significant decline i.e. less than 60% in case of BR in combination with oxacillin and penicillin at the initial 2h of incubation followed by AR and QT in combination with ampicillin. The study thus revealed potential antibacterial effects of berberine, artesunate, and quercetin along with significant resistance modulation in terms of highly synergistic combinations with antibiotics focused on novel insights into alternatives to antimicrobials to pave the road for antimicrobial stewardship against ailments like mastitis. [ABSTRACT FROM AUTHOR]

Background: Bacterial metabolites play a crucial role in human health and have proven effective in treating various diseases. In this study, the 16S rRNA method and streaking were employed to isolate and molecularly identify a bacterial strain, with the goal of characterizing bioactive volatile metabolites extracted using nonpolar and polar solvents. Methods: Gas chromatography-mass spectrometry (GC-MS) analysis was conducted to identify 29 compounds in the bacterial metabolites, including key compounds associated with Bacillus spp. The main compounds identified included 2-propanone, 4,4-ethylenedioxy-1-pentylamine, 1,2-benzenedicarboxylic acid, 1,1-butoxy-1- isobutoxy-butane, and 3,3-ethoxycarbonyl-5-hydroxytetrahydropyran-2-one. Results: The literature indicates the diverse biological and pharmacological applications of these compounds. Different concentrations of the metabolites from Bacillus species were tested for biological activities, revealing significant inhibitory effects on anti-diabetic activity (84.66%), anti-inflammatory activity (99%), antioxidant activity (99.8%), and anti-hemolytic activity (90%). Disc diffusion method testing also demonstrated a noteworthy inhibitory effect against tested strains. Conclusion: In silico screening revealed that 1,2-benzenedicarboxylic acid exhibited anticancer activity and promising drug-designing properties against epithelial glioblastoma cancer genes. The study highlights the potential of Bacillus spp. as a valuable target for drug research, emphasizing the significance of bacterial metabolites in the production of biological antibacterial agents. [ABSTRACT FROM AUTHOR]

The rise in prevalence and drug resistance in Staphylococcus aureus of dairy animals require an alternative to antibiotics. Nanoparticles particularly metallic nanoparticles are a wise approach to modulating drug resistance. The current study thus focuses on the replacement of antibiotics with ZnO, MgO, and Fe2O3 nanoparticles. To achieve this goal, 200 cattle milk samples were collected aseptically and screened for subclinical mastitis using the purposive sampling technique. Following Bergey's manual of determinative bacteriology, S.aureus was identified and antibiotic susceptibility was tested using clinical laboratory and standard institute guidelines. On the other hand, resistant strains were put to antibacterial testing assay against metallic nanoparticles both by well diffusion and broth microdilution method. To analyze the data, both probability and non-probability statistical tools were applied using SPSS version 22 of statistical software at 5% probability. The current study showed 24.56% of S. aureus positive from commercial dairy while the resistance of these isolates against gentamicin, enrofloxacin, levofloxacin, and vancomycin was found to be 50, 40, 30, 30%, respectively. On the other hand, a disc diffusion assay was concluded with 24.525±0.806 mm (ZnO) followed by 16.475±0.950mm (MgO) and 13.150±1.392mm (Fe2O3). MgO stood first to contribute lowest Minimum inhibitory concentration (MIC) (1.302±0.564 mg/mL) followed by Fe2O3 (2.930±1.691 mg/mL) and ZnO (3.906±0.000 mg/mL). MIC of ZnO was recorded to be 18.23±11.93 mg/mL, 15.63±0.0 mg/mL, 13.02±4.5 mg/mL, 7.81±6.77 mg/mL, 5.21±2.26 mg/mL, and (3.906±0.000 mg/mL) at 04, 08, 12, 16, 20 and 24th h of incubation. A similar trend was followed by other nanoparticles at different hours of incubation. The study thus concludes a rise in resistant strains of S. aureus in bovine milk while metallic nanoparticles as effective alternatives. [ABSTRACT FROM AUTHOR]

Alternative and modified therapeutic approaches are key elements in culminating antibiotic resistance. To this end, an experimental trial was conducted to determine the cytotoxicity and antibacterial potential of composites of magnesium oxide (MgO) nanoparticles and antibiotics stabilized in sodium alginate gel against multi-drug-resistant Staphylococcus aureus isolated from a houbara bustard. The characterization of preparations was carried out using X-ray diffraction (XRD), scanning transmissible electron microscopy (STEM), and Fourier-transform infrared spectroscopy (FTIR). The preparations used in this trial consisted of gel-stabilized MgO nanoparticles (MG), gel-stabilized tylosin (GT), gel-stabilized ampicillin (GA), gel-stabilized cefoxitin (GC), gel-stabilized MgO and tylosin (GMT), gel-stabilized MgO and cefoxitin (GMC), and gel-stabilized MgO and ampicillin (GMA). The study presents composites that cause a lesser extent of damage to DNA while significantly enhancing mitotic indices/phases compared to the other single component preparations with respect to the positive control (methyl methanesulphonate). It was also noted that there was a non-significant difference (p > 0.05) between the concentrations of composites and the negative control in the toxicity trial. Studying in parallel trials showed an increased prevalence, potential risk factors, and antibiotic resistance in S. aureus. The composites in a well diffusion trial showed the highest percentage increase in the zone of inhibition in the case of GT (58.42%), followed by GMT (46.15%), GC (40.65%), GMC (40%), GMA (28.72%), and GA (21.75%) compared to the antibiotics alone. A broth microdilution assay showed the lowest minimum inhibitory concentration (MIC) in the case of GMA (9.766 ± 00 µg/mL), followed by that of GT (13.02 ± 5.64 µg/mL), GMC (19.53 ± 0.00 µg/mL), GA (26.04 ± 11.28 µg/mL), GMT (26.04 ± 11.28 µg/mL), MG (39.06 ± 0.00 µg/mL), and GC (39.06 ± 0.00 µg/mL). The study thus concludes the effective tackling of multiple-drug-resistant S. aureus with sodium-alginate-stabilized MgO nanoparticles and antibiotics, whereas toxicity proved to be negligible for these composites. [ABSTRACT FROM AUTHOR]