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Polymyxin B octapeptide and polymyxin B heptapeptide are potent outer membrane permeability-increasing agents
Y Kimura1, H Matsunaga, M Vaara
1Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Abstract:
Polymyxin B octapeptide (PBOP) and polymyxin B heptapeptide (PBHP) were found to be effective permeabilizers of the outer membrane of Escherichia coli and Salmonella typhimurium. PBOP was as effective as polymyxin B nonapeptide (PMBN), the known very potent permeabilizer. As low a PBOP concentration as 1 microgram/ml sensitized E. coli to rifampicin by a factor of 100. Three micrograms of PBOP per ml was sufficient to sensitize this target to all the other tested hydrophobic antibiotics (erythromycin, fusidic acid, clindamycin, and novobiocin) by a factor of 30. Only a slightly higher (3-fold) concentration of PBHP was required for a similar sensitizing effect.
Insights
Polymyxin B octapeptide (PBOP) and heptapeptide (PBHP) effectively permeabilize bacterial outer membranes. These peptides enhance antibiotic efficacy against Gram-negative bacteria like E. coli.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- The outer membrane of Gram-negative bacteria presents a significant barrier to antibiotic penetration.
- Polymyxin B nonapeptide (PMBN) is a known potent permeabilizer, but its derivatives may offer improved properties.
- Understanding outer membrane permeabilization is crucial for developing new antimicrobial strategies.
Purpose of the Study:
- To evaluate the outer membrane permeabilization capabilities of Polymyxin B octapeptide (PBOP) and Polymyxin B heptapeptide (PBHP).
- To assess the synergistic effect of PBOP and PBHP with various hydrophobic antibiotics against Escherichia coli and Salmonella typhimurium.
Main Methods:
- Bacterial outer membrane permeabilization assays using PBOP and PBHP.
- Determination of minimum inhibitory concentrations (MICs) of antibiotics in combination with PBOP/PBHP.
- Quantitative assessment of bacterial sensitization to antibiotics.
Main Results:
- PBOP demonstrated potent outer membrane permeabilization, comparable to PMBN.
- PBOP significantly sensitized E. coli to rifampicin (100-fold) and other hydrophobic antibiotics (30-fold) at low concentrations.
- PBHP also showed effective sensitization, requiring only a slightly higher concentration than PBOP.
Conclusions:
- PBOP and PBHP are effective agents for increasing the permeability of Gram-negative bacterial outer membranes.
- These polymyxin derivatives hold promise for enhancing the efficacy of existing hydrophobic antibiotics, potentially overcoming resistance mechanisms.
- Further research into PBOP and PBHP could lead to novel therapeutic approaches against challenging bacterial infections.