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- Title
Scope and Limitations of Exploiting the Ability of the Chemosensitizer NV716 to Enhance the Activity of Tetracycline Derivatives against Pseudomonas aeruginosa.
- Authors
Draveny, Margot; Rose, Clémence; Pinet, Alexis; Ferrié, Laurent; Figadère, Bruno; Brunel, Jean-Michel; Masi, Muriel
- Abstract
The spread of antibiotic resistance is an urgent threat to global health that requires new therapeutic approaches. Treatments for pathogenic Gram-negative bacteria are particularly challenging to identify due to the robust OM permeability barrier in these organisms. One strategy is to use antibiotic adjuvants, a class of drugs that have no significant antibacterial activity on their own but can act synergistically with certain antibiotics. Previous studies described the discovery and development of polyaminoisoprenyl molecules as antibiotic adjuvants with an OM effect. In particular, the compound NV716 has been shown to sensitize Pseudomonas aeruginosa to tetracycline antibiotics such as doxycycline. Here, we sought to explore the disruption of OM to sensitize P. aeruginosa to otherwise inactive antimicrobials using a series of tetracycline derivatives in the presence of NV716. We found that OM disruption expands the hydrophobicity threshold consistent with antibacterial activity to include hydrophobic molecules, thereby altering permeation rules in Gram-negative bacteria.
- Subjects
PSEUDOMONAS aeruginosa; TETRACYCLINE; ANTIBACTERIAL agents; TETRACYCLINES; GRAM-negative bacteria; DRUG resistance in bacteria
- Publication
Molecules, 2023, Vol 28, Issue 11, p4262
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules28114262