Communication breakdown in Gram-negative pathogens: By means of AHL quorum quenching acylases

Bacteria do not live a mere reclusive life, but they are capable of engaging social behavior by talking to each other using chemicals as their languages. This communication termed as “Quorum sensing”, and appears to be their strategy to take a census of the population, and consecutively conduct a synchronized population behavior. The knowledge that quorum sensing is often indispensable for pathogenic bacteria for establishing infection, makes this system an interesting target for novel antibiotics. With an alarming rise of antibiotic-resistant bacteria, every promising strategy to alleviate bacterial infections is a great contribution in drug development research. The research presented in this thesis simulate two early stages of antibacterial development process: compound discovery and preliminary animal testing. We focused on the use of enzyme that can degrade the signaling molecule. The idea is to develop a potential antibacterial therapy that provokes less pressure for resistance. In the first study, two novel enzymes were discovered, and proven to be active in reducing bacterial infection in a simple invertebrate model. Further, we developed a lung infection model in mouse, that helped us to prove the efficacy of a well-studied enzyme from our research group. Although these enzymes do not kill the bacteria like the conventional antibiotics, they can delay the infection process and give more time to the immune system to clear the infections.