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Background: The spread of carbapenem-resistant Gram-negative bacteria, particularly those having the bla CTX-M-15 gene, has stimulated a global challenge for ß-lactam antimicrobial effectiveness. This study aims to identify commercially available compounds that demonstrate strong antibacterial properties with high efficacy and low toxicity to combat the increasing problem of antibiotic resistance. Methods: Virtual screening and molecular docking techniques were employed to generate a pharmacophore model based on the molecular structure. Eleven potential compounds were selected based on their IC50 values. Subsequently, a molecular docking approach was employed to select the best three small molecules for further comprehensive investigation. Moreover, absorption, distribution, metabolism, and excretion (ADME) and toxicity analysis ensured that it can be used as a drug without the effect of health. Finally, molecular dynamic (MD) simulations and generalized Born model and solvent accessibility (MMGB/SA) were carried out to evaluate the stability of these compounds against the receptor. Results: Three selected compounds, specifically ZINCCID (ZINC94211493, ZINC20528448, and ZINC04331046), have exhibited strong binding affinities of -8.4, -8.1, and -7.7 kcal/mol, respectively. This has been predicted as a potential competitive inhibitor targeting CTX-M-15. However, further assessment through experimental lab studies is required to evaluate the efficacy of these compounds. Conclusion: Initially, a structure-based model was constructed, and subsequently, molecular docking, MD simulation, ADMET analysis, and MMGB/SA were performed. Through the A-to-Z virtual screening process, the top three natural compounds were identified as potential lead molecules in the development of novel drugs targeting CTX-M-15 for combating Klebsiella infections. [ABSTRACT FROM AUTHOR]

The widespread use of insecticides poses a significant threat to the health and sustainability of honeybees (Apis mellifera). This study aimed to isolate, identify, and investigate the potential of honeybee gut bacterial strains in mitigating the detrimental effects of insecticides on honeybees and extending their lifespan. The efficacy of seven honeybee gut bacterial strains in reducing insecticide toxicity was evaluated. Through the identification of honeybee gut bacterial isolates using 16s rRNA, seven strains were identified, namely Priestia endophytica, Bacillus subtilis, Bacillus pumilus, Peribacillus frigoritolerans, B. subtilis, Bacillus pumilus, and Bacillus tequilensis. The experimental results revealed that bees treated with these gut bacteria significantly reduced oxidative stress markers and detoxification enzyme levels compared to untreated bees. Moreover, the treated bees demonstrated enhanced immune responses. The bees treated with deltamethrin + intestinal bacteria showed an increase in bees' lifespan to 6.33 days compared to a lifespan of 4 days with deltamethrin only. Similarly, bees treated with acetamiprid intestinal bacteria had further extended to 10.33 days compared to a lifespan of 7.67 days with acetamiprid. These findings suggest that using honeybee gut bacterial strains may serve as a sustainable strategy to mitigate the harmful impacts of insecticides on honeybees, thereby promoting their overall health and contributing to the preservation of pollination services and apiculture. Further research is warranted to elucidate the underlying mechanisms and optimize the application of these natural products in honeybee management practices. [ABSTRACT FROM AUTHOR]