Grant: Project Grant

Although bacteria can cause disease in humans (bad bacteria), most do not and can even be beneficial (e.g. microbiome). When harmful bacteria find their way in our body, the immune system is activated and clears the bad bacteria without affecting our microbiome. Occasionally, bacteria overcome our immune defenses which leads to a bacterial infection and requires medical treatment. Antibiotics are at the basis of modern medicine; they are used not only to cure bacterial infections but also to protect pre-term babies, AIDS patients, patients undergoing chemotherapy, hemodialysis or any surgery (e.g. C-section, biopsies, hip replacement, introducing a stent etc.). Antibiotics save millions of lives every year. Unlike our immune system, however, antibiotics kill not only the bad bacteria but also those that make up our microbiome, leading to side effects such as diarrhea. Since the discovery of antibiotics and their use in the clinic, humans and bacteria have become locked in an arms race: as we develop new antibiotics the bacteria evolve resistance to them. Therefore antibiotics have a finite useful lifespan and most do not work well anymore. We definitely need new antibiotics, however, to end the arms race we must learn to treat infections without antibiotics. We propose to replace antibiotics with bacterio-modulators, which we define as molecules that make bacteria more susceptible to our immune system. This results in our immune defenses selectively killing the bad bacteria without causing harm to our microbiome. We have reported a proof-of-principle study demonstrating the efficacy of some bacterio-modulators towards Salmonella. We propose here not only to expand on this study but also to adapt it to other pathogens such as tuberculosis, a disease which kills >1.5 million people annually in the world. Once this concept is demonstrated with tuberculosis, we believe that it will rapidly be adapted to other infectious diseases and will revolutionize modern medicine.