Using Small-Molecule Adjuvants to Repurpose Azithromycin for Use against Pseudomonas aeruginosa.
Veronica B HubbleBrittany A HubbardBradley M MinrovicRoberta J MelanderRoberta J MelanderPublished in: ACS infectious diseases (2018)
A major contributor to fatalities in cystic fibrosis (CF) patients stems from infection with opportunistic bacterium Pseudomonas aeruginosa. As a result of the CF patient's vulnerability to bacterial infections, one of the main treatment focuses is antibiotic therapy. However, the highly adaptive nature of P. aeruginosa, in addition to the intrinsic resistance to many antibiotics exhibited by most Gram-negative bacteria, means that multi-drug-resistant (MDR) strains are increasingly prevalent. This makes the eradication of pseudomonal lung infections nearly impossible once the infection becomes chronic. New methods to treat pseudomonal infections are greatly needed in order to eradicate MDR bacteria found within the respiratory tract, and ultimately better the quality of life for CF patients. Herein, we describe a novel approach to combatting pseudomonal infections through the use of bis-2-aminoimidazole adjuvants that can potentiate the activity of a macrolide antibiotic commonly prescribed to CF patients as an anti-inflammatory agent. Our lead bis-2-AI exhibits a 1024-fold reduction in the minimum inhibitory concentration of azithromycin in vitro and displays activity in a Galleria mellonella model of infection.
Keyphrases
- cystic fibrosis
- pseudomonas aeruginosa
- end stage renal disease
- drug resistant
- small molecule
- chronic kidney disease
- newly diagnosed
- ejection fraction
- multidrug resistant
- peritoneal dialysis
- respiratory tract
- anti inflammatory
- climate change
- acinetobacter baumannii
- ionic liquid
- bone marrow
- air pollution
- artificial intelligence
- helicobacter pylori infection
- cell therapy