**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** AS A VALUABLE AND NECESSARY POLLINATOR OF MAJOR AGRICULTURAL COMMODITIES, HONEY BEES CONTRIBUTE OVER 20 BILLION ANNUALLY TO THE GDP. HONEY BEE POPULATIONS MANAGED FOR THESE PURPOSES HAVEREQUIRED MUCH GREATERRESOURCE INVESTMENT TO MAINTAIN POPULATION SIZE, AND KNOWN AND UNKNOWN LARVAL DISEASE HAS BECOME PREVALENT AS ONE POTENTIAL CAUSE OF COLONY LOSS.MANAGED HONEY BEES ARE HIGHLY SOCIAL, FREQUENT A MULTITUDE OF ENVIRONMENTAL NICHES, AND CONTINUALLY SHARE FOOD, CONDITIONS THAT PROMOTE THE TRANSMISSION OF PARASITES AND PATHOGENS. ADDITIONALLY, COMMERCIAL HONEY BEES USED IN AGRICULTURE ARE STRESSED BY CROWDING AND FREQUENT TRANSPORT, AND EXPOSED TO A PLETHORA OF AGRICULTURAL CHEMICALS AND THEIR ASSOCIATED BYPRODUCTS. SIMILAR TO OTHER LIVESTOCK, THEY ARE ALSO FED ANTIBIOTICS, OFTEN WHEN THEY HAVE NO SIGN OF DISEASE. AS WE HAVE LEARNED FROM THE HOSPITAL SETTING, THIS INEVITABLY LEADS TO THE DEVELOPMENT OF HIGHLY ANTIBIOTIC RESISTANT BACTERIAL PATHOGENS. WHEN CONSIDERING THIS PROBLEM, THE HIVE OF THE HONEY BEE MAY BE BEST CHARACTERIZED AS AN EXTENDED ORGANISM THAT NOT ONLY HOUSES DEVELOPING YOUNG AND NUTRIENT RICH FOOD STORES, BUT ALSO PROVIDES AN ENVIRONMENT FOR SYMBIOTIC MICROBIAL COMMUNITIES THAT PRIMARILY DEFEND AGAINST PATHOGENS. THEMAINTENANCE OF THESE BENEFICIAL HONEY BEE SYMBIONTS IS LARGELY UNKNOWN, AS ARE THE WAYS IN WHICH SUCH COMMUNITIES CONTRIBUTE TO HONEY BEEIMMUNITY, AND OVERALL HEALTH. A SYSTEMS VIEW FOCUSED ON THE INTERACTION OF THE HONEY BEE WITH ITS ASSOCIATED MICROBIAL COMMUNITY IS NEEDED TO UNDERSTAND THE GROWING AGRICULTURAL CHALLENGES FACED BY THIS ECONOMICALLY IMPORTANT ORGANISM. THE ROAD TO SUSTAINABLE HONEY BEE POLLINATION LIES BEYOND THE CRUDE APPLICATION OF ANTIBIOTICS, AND WILLEVENTUALLY REQUIRETHE INTEGRATED UNDERSTANDING AND INFORMED MANAGEMENT OF HONEY BEE MICROBIAL SYSTEMS.USING MODERN MOLECULAR METHODS, WE WILL IDENTIFY THE ENTIRE SET OF MICROBES ASSOCIATED WITH LARVAL HEALTH AND DISEASE IN THE HONEY BEE COLONY. WE WILL FURTHER IDENTIFY THE MOLECULAR FACTORS RESPONSIBLE FOR THE PROMOTION OFVARIOUS DISEASE STATES, AND DISTINGUISH THESE FROM PROTECTIVE MICROBES AND COMPROMISED HOST HEALTH. OUR APPROACH WILL INCLUDE BOTH A LAB COMPONENT AND FIELD COMPONENT THAT WORK COLLECTIVELY TO PROVIDE INFORMATION ON DISEASE PROGRESSION, PREVALENCE AND DISTRIBUTION. MICROBES WILL BE COLLECTED FROM THE FIELD ASSAYS, AND USED IN LAB EXPERIMENTS THAT REVEAL THE DISEASE CAUSING POTENTIAL OF THE MICROBE UNDER VARIOUS ENVIRONMENTAL CONDITIONS. OUR RESULTS WILL REVEAL THE VARIOUS TYPES AND CAUSES OF BROOD DISEASE, AND NEW INSIGHT INTO THE ROLE OF BENEFICIAL OR ASSOCIATED MICROBESIN HEALTH OR DISEASE PROGRESSION.THIS WORK WILL ESTABLISH THE LARGEST AND MOST INCLUSIVE PUBLICALLY AVAILABLE DATASET OF MICROBES AND CONDITIONS ASSOCIATED WITH LARVAL DISEASE, AND THEIR POTENTIAL TO CAUSE DISEASE BOTH ALONE AND IN COMBINATION WITH OTHER MICROBES AND ENVIRONMENTAL CONDITIONS. THIS DATA WILL BE USED TO IMPROVE DIAGNOSTIC CAPABILITY AND TRACK THE RECURRENCE AND EMERGENCE OF NEW MICROBIAL STRAINS NATION-WIDE THAT MAY AFFECT HONEY BEE HEALTH.THE RESULTS WILL PROVIDE PREDICTIVE TOOLS BASED ON THE FACTORS THAT OFTEN LEAD TO MAJOR BACTERIAL DISEASES, AND IMPROVE OUR GENERAL KNOWLEDGE OF PEST AND PATHOGEN BIOLOGY.THE FINAL RESULT WILL BE IMPROVED PEST AND PATHOGEN MANAGEMENT TOOLS FOR BEEKEEPERS WITH A FOCUS ON DIAGNOSTICS, IMPROVED PRACTICES, AND A STRONG INFORMATIONAL CONTEXT FOR DEVELOPING TREATMENTS.