- 作者: Hala A. Farrag, Nagwa Abdallah, Mona M. K. Shehata and Ebthag M. Awad
- 作者服務機構: 1. Drug Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, P.O. Box 29, Nasr City, Cairo, Egypt 2. Microbiology Department, Faculty of Science, Ain Shams University, Cairo, Egypt
- 中文摘要:
- 英文摘要:
Background
This study sought to develop new strategies for reverting the resistance of pathogenic Gram-negative bacilli by a combination of conventional antibiotics, potent permeabilizers and natural beta lactamase inhibitors enhancing the activity of various antibiotics.
Methods
The antibiotic susceptibility in the presence of natural non-antibacterial tested concentrations of phytochemicals (permeabilizers and natural beta lactamase inhibitors) was performed by disk diffusion and susceptibility assays. Thymol and gallic acid were the most potent permeabilizers and facilitated the passage of the antibiotics through the outer membrane, as evidenced by their ability to cause LPS release, sensitize bacteria to SDS and Triton X-100.
Results
The combination of permeabilizers and natural beta lactamase inhibitors (quercetin and epigallocatechin gallate) with antibiotics induced greater susceptibility of resistant isolates compared to antibiotic treatment with beta lactamase inhibitors alone. Pronounced effects were detected with 24.4 Gy in vitro gamma irradiation on permeability barrier, beta lactamase activity, and outer membrane protein profiles of the tested isolates.
Conclusions
The synergistic effects of the studied natural phytochemicals and antibiotics leads to new clinical choices via outer membrane destabilization (permeabilizers) and/or inactivation of the beta lactamase enzyme, which enables the use of older, more cost-effective antibiotics against resistant strains. - 中文關鍵字:
- 英文關鍵字: Pathogenic gram-negative bacilli, Outer membrane permeability, Beta lactam resistance, Permeabilizers, Natural beta lactamase inhibitors, In vitro gamma irradiation