Bafilomycin A1 as a host-directed treatment for bacterial infection

Salmonella Typhimurium (STm) is a type of bacteria that causes the foodborne illness Salmonellosis, leading to millions of illnesses each year. This disease can be quite severe and even deadly, especially in children who account for the majority of cases. It a major health concern worldwide, especially with the rise of drug-resistant strains that don't respond to antibiotics. Drug resistance can occur after repeated exposure to drugs, pressuring bacteria mutate and adapt in ways that allow them to survive the antibiotics. Additionally, some bacteria are naturally highly resistant and difficult to treat. Experts predict that by 2050, drug-resistant infections could cause 40 million deaths. To fight this, our lab is exploring a new treatment method called host-directed therapy (HDT). Rather than targeting the bacteria directly with antibiotics, HDT boosts the body's immune system to fight off infections. We have discovered that a compound called bafilomycin A1 (bafA1) can kill over 99% of STm hidden within human cells, without harming the immune cells. This success rate is comparable to what we see with current antibiotics. My research aims to understand how bafA1 works to kill STm in our cells, and to test if it also effective against other dangerous, drug-resistant bacteria like Mycobacterium tuberculosis, which causes Tuberculosis and Listeria monocytogenes, which causes the foodborne illness Listeriosis. I believe that bafA1 activates certain pathways in immune cells that can be used as a treatment to fight these hard-to-treat infections. Ultimately, bafA1 could be a promising tool in the fight against antibiotic-resistant bacteria, helping to improve treatments and slow the spread of resistance.