Publication Date
8-2024
Advisor(s) - Committee Chair
Ali Er, Ivan Novikov, Simran Banga
Degree Program
Department of Physics and Astronomy
Degree Type
Master of Science
Abstract
Efflux pumps are critical active transport systems utilized by cells to expel toxic substances, including antibiotics and photosensitizer complexes, thereby contributing to antimicrobial resistance. Efflux pump inhibitors (EPIs), which are compounds that obstruct the transport of molecules through these pumps, play a pivotal role in enhancing the effectiveness of antimicrobial therapies against pathogens. This study investigates the effects of the EPI reserpine on the photodeactivation rate of pathogens when used in conjunction with silver nanoparticles (Ag NPs) and methylene blue (MB), a common photosensitizer.
Our research reveals that the application of reserpine, in combination with Ag NPs and MB, leads to a significantly higher rate of pathogen deactivation compared to the use of Ag NPs and MB alone. This enhanced deactivation rate suggests that reserpine plays a crucial role in disrupting the cellular mechanisms that typically expel these toxic agents. To understand the underlying mechanisms, we examined the generation of singlet oxygen, a reactive oxygen species known to play a role in photodeactivation.
Additionally, we tested different sizes of Ag NPs in combination with reserpine to determine if nanoparticle size influences the effectiveness of this treatment. The results indicate that reserpine consistently improves the deactivation rate, regardless of the size of the Ag NPs. Molecular docking calculations were performed to investigate the affinity of reserpine and MB for the AcrB protein, a component of the AcrAB-TolC efflux pump. These calculations demonstrated that reserpine has a higher affinity for AcrB compared to MB.
The significant improvement in bacterial deactivation observed in our study is primarily attributed to the blockage of the AcrAB-TolC efflux pump by reserpine. This blockage prevents the removal of MB from the cells, thereby enhancing the photodeactivation process. The increased deactivation rate is not due to enhanced singlet oxygen production, but rather the effective retention of MB within the cells.
Disciplines
Biological and Chemical Physics | Biophysics | Microbiology | Other Microbiology | Physics
Recommended Citation
Allamyradov, Yaran, "THE ROLE OF EFFLUX PUMP INHIBITOR IN ENHANCING ANTIMICROBIAL EFFICIENCY OF SILVER NANOPARTICLES AND METHYLENE BLUE AS AN EFFECTIVE PHOTODYNAMIC THERAPY AGENT" (2024). Masters Theses & Specialist Projects. Paper 3756.
https://digitalcommons.wku.edu/theses/3756