Controlling Antibiotic Resistance by Vaccinating Bacterial Populations

The prevalence of antibiotic resistant bacteria has risen dramatically over the past decades with over 70% of hospital bacterial infections harboring resistance to one or more classes of antibiotics. To date, the rise of drug resistant pathogens has been addressed by improved containment practices, judicious use of antibiotic treatments, and government-sponsored antibiotic research and development programs. Despite these measures, we are still facing a losing battle against the spread of antibiotic resistance. Given these significant challenges, both technical and economic, new strategies for combating antibiotic resistance are desperately needed. We propose a novel strategy that will limit the occurrence and spread of antibiotic resistance by targeting the genetic elements that encode antibiotic resistance, rather than any particular microbial species or strain. The approach is therefore broadly applicable to both Gram-positive and negative bacteria. To achieve this goal, we propose to use engineered mobile genetic elements to"vaccinate"microbial communities against uptake and dissemination of genetically-encoded antibiotic resistance elements. This approach is now made possible by technology advances in synthetic biology centered around gene and genome design and construction.