Salmochelin-antibiotic conjugates target pathogenic gram-negative bacteria and can be used for therapeutic treatment in humans and other animals.
Antibiotic resistance has long been a cause for concern in the microbiology community. Most conventional methods of countering the development of resistance focus on the creation of new antibiotics that target intracellular processes; however, gram-negative bacteria possess an outer membrane that acts as a barrier to antibiotic entry. Spontaneous mutations in these membranes provide gram-negative bacteria new methods of antibiotic resistance. A novel method for the intracellular delivery of existing antibiotics may provide an additional means of targeting pathogenic gram-negative bacteria that bypasses the outer membrane barrier.
This invention involves a modified version of salmochelin, which is expressed in pathogenic gram-negative bacteria and which contributes to their pathogenicity. Salmochelin is a siderophore used by these pathogenic bacteria to scavenge for extracellular iron. Receptors on the outer membrane bind to salmochelin and facilitate the delivery of iron into the cytosol. In this invention, the salmochelin is linked to antibiotics with polyetheylene glycol linkers. The modified salmochelin binds to receptors on the cell membrane and delivers its conjugated antibody into the bacteria. Modified salmochelin is advantageous to non-native antibiotic models because its mechanism of delivery involves native cell machinery. This allows for enhanced recognition and delivery. Moreover, modified salmochelin can easily be adapted to deliver non-antibiotic entities into pathogens, such as other toxic molecules, or even fluorophores or biotin.
Related to Technology #16976, Sidophore-Based Immunization Against Gram-Negative Bacteria.
Combats the development of antibiotic resistance, which occurs when the outer membrane in gram-negative pathogens undergo spontaneous mutation
Specific targeting of pathogenic bacteria compared to commensal bacteria
Exploitation of native cell machinery to deliver antibiotics
Capability of delivering non-antibiotic constructs into pathogens as well