Antimicrobial resistance (AMR) towards medicine has been an ongoing concern for the last several decades. The concept that a microbe can build resistance and multiply faster than scientists can find a treatment is becoming more of a reality. Since the discovery of penicillin by Dr. Alexander Fleming in 1928, various bacterial infections have slowly become resistant to therapies. Unfortunately, 1.27 million deaths a year are associated with AMR. As a result, drug-resistant bacterial infections pose a greater threat to the world than other widespread illness, including HIV or Malaria.
To overcome AMR, many researchers are working to disable bacterial mechanisms and sensitize colonies to drug treatments. A recent article in Cell Biomaterials, by Dr. Hydar Ali and others, found a new way to appropriately treat drug-resistant microbes. Ali is Professor and Associate Dean for Faculty Development and Mentorship in the Department of Basic & Translational Sciences at the University of Pennsylvania (UPenn). His work focuses on immune cell host response and chronic inflammatory disease. Specifically, through his work he tries to understand how the immune system initially responds to pathogens and allergies.
Ali and his team discovered various proteins that can destroy bacterial membranes. Interestingly, these proteins do not only kill drug-resistant bacteria but can trigger a strong immune response. Interestingly, these proteins are mirror images of the protein building blocks in the body known as L-amino acids. What makes these peptides more effective is that their position, which is flipped from the original L-amino acids, allows the proteins to go undetected by digestive enzymes. Therefore, the proteins stay intact longer and can generate stronger efficacy compared to previous drugs.
The team used culture dishes to observe how these peptides eliminate bacteria and initiate an immune response. Interestingly, the peptides ripped the protective bacterial membranes of a resistant group of pathogens. In addition to this specific attack on bacteria, the peptides or proteins also bound to innate immune cells. These specific cells are the first immune cells on scene of an infection and initiate further host immunity. Once the peptides bound themselves to the immune cells, various molecules and signals were released to elicit more immune cell trafficking to the infection and destroy the present bacteria.
The two-part treatment provides direct elimination of pathogens but initiates the innate immune response. The immune cells the treatment binds to are known as mast cells, which are abundant on the skin and protect against many different infections. What is special about this treatment is that it amplifies mast cell reaction and signals to the body that there is a deadly pathogen present. Previously, what made some bacterial infections so dangerous is their ability to go undetected or elicit a immune response. Once the mast cells send out a signal to the body, other immune cells will navigate to the site of infection and clear the dead bacteria and eliminate any other living colonies present. These results were repeated and confirmed in studies conducted with mice.
The discovery of these peptides effectively targets AMR. In this case, the bacteria will have to overcome two hurdles including, (1) direct bacteria death and (2) a strong immune response. As a result, this approach would slow AMR and improve treatment of bacterial infection. Further testing is underway to confirm efficacy and optimize the regimen before testing the therapy in clinical trials.
