Related Experiment Videos
The outer membrane permeability-increasing action of deacylpolymyxins
P Viljanen1, H Matsunaga, Y Kimura
1Department of Fisheries, Faculty of Agriculture, Miyazaki University, Japan.
Abstract:
The outer membrane permeability-increasing action of deacylpolymyxins was compared to the well-known potent action of polymyxin B nonapeptide (PMBN). Deacylpolymyxin B (DAPB), prepared by treating polymyxin B with polymyxin acylase, was found to be a slightly more effective permeabilizer than PMBN. As low a DAPB concentration as 1 microgram/ml sensitized Escherichia coli to the probe antibiotics (rifampin, fusidic acid, erythromycin, clindamycin, novobiocin) by factors 30-100 and Salmonella typhimurium by factors 10-100. A higher concentration (3 micrograms/ml) of DAPB elicited further sensitization. Also deacylcolistin (DAC) was found to be an effective permeabilizer.
Insights
Deacylpolymyxins, like deacylpolymyxin B (DAPB), are potent outer membrane permeabilizers, enhancing antibiotic effectiveness against bacteria like Escherichia coli and Salmonella typhimurium.
Area of Science:
- Microbiology
- Drug Discovery
- Antimicrobial Resistance
Background:
- Polymyxins are crucial antibiotics targeting Gram-negative bacteria.
- Outer membrane permeability is a key factor in antibiotic efficacy.
- Polymyxin B nonapeptide (PMBN) is a known potent permeabilizer.
Purpose of the Study:
- To compare the outer membrane permeability-increasing activity of deacylpolymyxins with PMBN.
- To evaluate the effectiveness of deacylpolymyxin B (DAPB) and deacylcolistin (DAC) as permeabilizers.
Main Methods:
- Deacylpolymyxin B (DAPB) was prepared by treating polymyxin B with polymyxin acylase.
- Bacterial sensitization assays were performed using probe antibiotics (rifampin, fusidic acid, erythromycin, clindamycin, novobiocin).
- Comparative analysis of DAPB and PMBN as outer membrane permeabilizers.
Main Results:
- DAPB demonstrated slightly higher permeabilizing activity than PMBN.
- Low concentrations of DAPB (1 microgram/ml) significantly sensitized Escherichia coli (30-100 fold) and Salmonella typhimurium (10-100 fold) to antibiotics.
- Higher DAPB concentrations (3 micrograms/ml) resulted in further sensitization.
- Deacylcolistin (DAC) was also identified as an effective permeabilizer.
Conclusions:
- Deacylpolymyxins, particularly DAPB, are highly effective agents for increasing outer membrane permeability.
- DAPB shows promise as a sensitizer to enhance the efficacy of existing antibiotics against Gram-negative bacteria.
- Further research into deacylpolymyxins could lead to novel strategies for combating antimicrobial resistance.