Bacterial pathogens cause substantial loss of life worldwide
In the Baylink lab we are investigating the disease mechanisms of bacterial pathogens to identify new strategies to control infections. Our current areas of study include the gastrointestinal pathogens Helicobacter pylori, a causative agent of stomach cancer, and Salmonella enterica, a major cause of diarrheal disease and suspected cause of inflammatory bowel diseases.
H. pylori and S. enterica stimulate inflammation as part of their infection strategy, which can progress to states of chronic inflammation and cancers. Together, these bacterial pathogens are associated with over a million deaths worldwide every year.
Multi-drug resistance on the rise
Drug-resistant strains of H. pylori and S. enterica are designated as ‘priority pathogens’ by the World Health Organization, and require immediate development of new antibacterial strategies.
A recent study of H. pylori in China illustrates the concerning rate of resistance against antibiotics.
Metronidazole-resistant
Levofloxacin-resistant
Clarithromycin-resistant
Tetracycline-resistant
Amoxicillin-resistant
Where will we find the next generation of antibacterial medicines?
Our research group is studying the potential of targeting bacterial redox defenses as a novel way to combat bacterial infections. During infection a redox battle is waged between our immune cells and bacteria. Infiltrating phagocytes catalyze high concentrations of reactive electrophilic species (RES) such as hypochlorous acid (HOCl) and hydroperoxides (ROOH) that can kill bacteria through oxidizing bacterial proteins, lipids, and nucleic acids.
However, bacteria possess highly efficient antioxidant enzymes that can rapidly clear RES, helping them survive and persist. In the Baylink lab we determine the molecular structures of these enzymes, study their function, and learn how to inhibit them.
Below is the structure of a peroxiredoxin enzyme from Salmonella enterica serovar Typhimurium. These enzymes convert hydroperoxides to water. Using protein crystallography we study how bacterial redox defenses operate at the atomic level and learn how they perform their essential chemical reactions.
By understanding the fundamentals of how bacterial redox defenses operate, and their molecular structures, we can employ Virtual Ligand Screening to computationally screen millions of drug-like compounds. Promising compounds can then be tested for binding and antibacterial activity.
To take these new drug leads to the next stages of development, Dr. Baylink founded the company Amethyst Antimicrobials, LLC. Amethyst partners with academic endeavors and will be funded through opportunities such as SBIR/STTR awards available through NIH.
