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Effect of permeabilizers on antibiotic sensitivity of Pseudomonas aeruginosa
H M Ayres1, J R Furr, A D Russell
1Welsh School of Pharmacy, Cardiff University, UK.
Abstract:
Agents which had previously been shown to act as permeabilizers against Pseudomonas aeruginosa or other Gram-negative bacteria were tested to determine whether susceptibility to various antibiotics could be increased. In the absence of a permeabilizer, Ps. aeruginosa was resistant to several hydrophobic antibiotics and vancomycin, but not to gentamicin. Tartaric and gluconic acids had weak potentiating activity, whereas ethylenediamine tetraacetic acid and citric acid were more effective permeabilizers. However, sodium polyphosphate enhanced the activity of erythromycin, fucidin, novobiocin, rifampicin and methicillin; vancomycin was unaffected and the activity of gentamicin was reduced considerably.
Insights
Certain agents can increase antibiotic effectiveness against Pseudomonas aeruginosa. Sodium polyphosphate notably boosted several antibiotics, while others showed varied results, offering new strategies for combating Gram-negative bacterial infections.
Area of Science:
- Microbiology
- Pharmacology
- Bacterial Pathogenesis
Background:
- Pseudomonas aeruginosa is a Gram-negative bacterium known for its intrinsic resistance to many antibiotics.
- Developing strategies to overcome antibiotic resistance in Gram-negative pathogens is a critical area of research.
- Permeabilizers are agents that can disrupt bacterial outer membranes, potentially increasing antibiotic susceptibility.
Purpose of the Study:
- To evaluate the ability of known permeabilizing agents to enhance the efficacy of various antibiotics against Pseudomonas aeruginosa.
- To identify specific agents that can potentiate antibiotic activity against this resistant Gram-negative bacterium.
Main Methods:
- Testing of agents previously identified as permeabilizers against Gram-negative bacteria.
- Assessment of changes in Pseudomonas aeruginosa susceptibility to antibiotics including hydrophobic agents and vancomycin.
- Comparative analysis of the effects of tartaric acid, gluconic acid, ethylenediamine tetraacetic acid, citric acid, and sodium polyphosphate.
Main Results:
- In the absence of permeabilizers, Pseudomonas aeruginosa exhibited resistance to hydrophobic antibiotics and vancomycin but not gentamicin.
- Ethylenediamine tetraacetic acid and citric acid demonstrated effective permeabilizing activity.
- Sodium polyphosphate significantly enhanced the activity of erythromycin, fucidin, novobiocin, rifampicin, and methicillin, but did not affect vancomycin and reduced gentamicin activity.
Conclusions:
- Specific permeabilizing agents can modulate antibiotic susceptibility in Pseudomonas aeruginosa.
- Sodium polyphosphate shows promise in potentiating a range of antibiotics against this Gram-negative pathogen.
- Further research into permeabilizer-antibiotic combinations may offer novel therapeutic approaches for resistant bacterial infections.