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ANTIBIOTIC RESISTANCE IS INCREASING AT AN ALARMING RATE. THE LACK OF ALTERNATIVES FOR ANTIBIOTICS THREATENS A POST-ANTIBIOTIC FUTURE, WHERE PREVIOUSLY TREATABLE DISEASES ARE NO LONGER TREATABLE. BACTERIA'S NATURAL PREDATOR, BACTERIOPHAGES (PHAGES), ARE BECOMING AN INCREASINGLY ATTRACTIVE ALTERNATIVE TO ANTIBIOTICS. PHAGES ARE VIRUSES THAT INFECT BACTERIAL HOSTS FOR THE PURPOSE OF REPLICATING. THE INFECTION CYCLE'S FINAL STEP KILLS THE HOST CELL AND RELEASES THE NEWLY REPLICATED PHAGES INTO THE ENVIRONMENT TO REPEAT THE PROCESS. ANOTHER ATTRACTIVE ANTIMICROBIAL IS BACTERIOCINS, WHICH ARE TOXINS PRODUCED BY BACTERIA TO OUTCOMPETE CLOSELY RELATED STRAINS. PHAGES AND BACTERIOCINS ARE NATURALLY ABUNDANT AND DIVERSE, THUS OFFERING A SEEMINGLY ENDLESS RESERVOIR OF POTENTIAL ANTIMICROBIAL CANDIDATES; HOWEVER, THEY ARE BOTH SUSCEPTIBLE TO RESISTANCE. THEREFORE, THE OVERARCHING ISSUE OF ANTIMICROBIAL RESISTANCE IS A PUBLIC HEALTH ISSUE.TO ADDRESS AMR, THIS PROJECT PROPOSES AN ANTIMICROBIAL SYSTEM THAT IS LESS PRONE TO RESISTANCE. THIS ANTIMICROBIAL SYSTEM COMBINES THE KILLING POWER OF PHAGES AND BACTERIOCINS USING GENETIC ENGINEERING. WHEN COMPARED TO THE RESISTANCE RATE OF THE PHAGE AND BACTERIOCIN ACTING ALONE, THIS SYSTEM RATE IS EXPECTED TO LOWER.THE CORE PREMISE BEHIND THIS IDEA IS HURDLE TECHNOLOGY. FOR A BACTERIAL CELL TO SURVIVE THIS TREATMENT, IT WOULD NEED TO DEVELOP TWO SEPARATE RESISTANCE MECHANISMS (ONE FOR EACH ANTIMICROBIAL). AS SUCH, THE RATE OF RESISTANCE FOR THIS SYSTEM (DOUBLE HURDLE) IS EXPECTED TO BE LOWER THAN THAT OF THE INDIVIDUAL ANTIMICROBIALS (SINGLE HURDLE). THE NUMBER OF PHAGES AND BACTERIOCINS COMBINATIONS IN THIS SYSTEM SEEM INFINITE WHEN CONSIDERING THE NATURAL DIVERSITY OF PHAGES AND BACTERIOCINS COMBINATIONS. WITH THAT IDEA IN MIND, THIS PROJECT EXAMINES HOW THE NUMBER OF HURDLES (TRIPLE, DOUBLE, AND SINGLE) AND TYPE OF HURDLE (BACTERIOCIN, PHAGE) IMPACTS RESISTANCE USING GENETIC ENGINEERING AND WHOLE-GENOME SEQUENCING.FROM THE DATA GENERATED, A LEARNING MODULE USING THIS PROJECT AS A CASE STUDY WILL BE DEVELOPED FOR A SECONDARY STEM CURRICULUM. ITS GOAL IS TO EQUIP HIGH SCHOOL STUDENTS WITH THE FOUNDATIONAL KNOWLEDGE REQUIRED TO APPRECIATE THE SEVERITY OF AMR AND HOW BIOTECHNOLOGY IS USED TO ADDRESS IT. BY MAKING AMR RESEARCH MORE ACCESSIBLE, THE LEARNING MODULE WILL PROMOTE AMR STEWARDSHIP AND, HOPEFULLY, INSPIRE THE NEXT GENERATION OF AMR RESEARCHERS.

$120,000FY2022National Institute of Food and AgricultureUSDA

Cornell University, Ithaca NY

Investigators

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