Grant: Project Grant

Just like antibiotic resistance genes render bacteria unresponsive to traditional antibiotic therapy, there are bacterial gene products that have evolved to weaken our natural host defenses. These anti-immunity genes carried by bacteria confer intrinsic susceptibility to individuals during infection because of their neutralizing effects on our normally robust systems of immunity. This Project Scheme application builds on 10 years of research towards a comprehensive understanding of how enteric pathogens overcome host immunity by integrating a spectrum of virulence and fitness genes during host infection. Born out of our pioneering work on regulatory evolution as a mechanism of pathogen emergence, we have identified bacterial virulence proteins that inhibit natural host defense systems. Importantly, we have shown that these immune antagonists can be blocked to restore natural host immunity, even against drug-resistant organisms. Therefore, we believe there are strategies to re-sensitize pathogens to our innate immune system and create novel opportunities in anti-infective medicine. Using new technologies in genomics and microbial chemical biology, we are creating an unprecedented opportunity for insight into the interface of human and microbial biology that is informing novel strategies to combat infections and drug resistance. This knowledge base creates opportunities for innovative drug target discovery with tangible impact into public health.