Abstract
Most Gram-negative bacteria are naturally resistant to many existing antibiotics because of the nature of their double membrane envelope. Many antibiotics need to gain access to the cytoplasm in order to be effective against Gram-negative bacteria. Resistance to antibiotics can also develop due to bacteria taking advantage of the space between the two membranes to export the drug out before it enters the cytoplasm. To overcome this problem, the understanding of mechanisms for the cellular entry for molecules across the membranes is vital. Iron, an essential element for life, is necessary for many metabolic enzymes. Successful pathogenic bacteria have evolved mechanisms to scavenge iron from their environment and transport it inside their cells. They synthesize specialized molecules with very high affinity for iron called siderophores. There are some reports describing the transport of siderophores across membranes by tagging them with fluorescent dyes. This methodology has recently spurred interest in investigating similar Trojan-horse approaches to transport antibiotics across the double membranes of Gram-negative bacteria. There are two critical elements to the design of such molecules. First, the attached molecule should not interfere with the transport mechanism. Second, the release of the antibiotic in the cytoplasm is possible after crossing the membrane through a cleavable linker. While the ability of pyochelin to chelate iron and other metal ions is well documented, its potential as a means of more efficiently transporting antibiotics into bacteria has not been fully explored. We are exploring the possibility to utilize pyochelin as a Trojan horse to transport antibiotics into the cytoplasm. Towards this goal, we have synthesized pyochelin using standard organic synthesis. This poster highlights our synthetic efforts to make Pyochelin and also the design and introduction of a cleavable linker. In the future, we will compare the effectiveness of common antibiotics using this delivery mechanism.
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Metadata
- Subject
Chemistry & Biochemistry
- Institution
Gainesville
- Event location
MPR 3
- Event date
22 March 2019
- Date submitted
19 July 2022
- Additional information
Acknowledgements:
Dr.Shailesh Ambre