THE GRAM-NEGATIVE BACTERIAL PATHOGEN EDWARDSIELLA ICTALURI CAUSES ENTERIC SEPTICEMIA OF CATFISH (ESC), AN ECONOMICALLY SIGNIFICANT DISEASE OF FARMED-RAISED CHANNEL CATFISH, ICTALURUS PUNCTATUS. VACCINATION HAS BECOME AN IMPORTANT ASPECT OF CONTROLLING BACTERIAL DISEASE IN SOME FISH, PARTICULARLY FOR COLD WATER PATHOGENS. DESPITE CONSIDERABLE EFFORT, HOWEVER, VACCINATION IS NOT WIDESPREAD FOR PREVENTION OF MICOBIAL DISEASES IN WARM-WATER FISH, ESPECIALLY CHANNEL CATFISH. THE ULTIMATE GOAL OF THE WORK PROPOSED HERE IS TO DEVELOP AN EFFECTIVE LIVE-ATTENUATED VACCINE USING KNOWLEDGE GAINED CONCERNING THE EFFECTOR PROTEINS OF THE TYPE THREE SECRETION SYSTEM (T3SS) OF E. ICTALURI. BACTERIAL T3SS ARE SOPHISTICATED PROTEIN MACHINES COMPRISED OF 30 OR MORE PROTEINS THAT FORM A NEEDLE LIKE STRUCTURE THAT SPANS THE BACTERIAL ENVELOPE AND TRANSLOCATES EFFECTOR PROTEINS DIRECTLY FROM THE BACTERIAL CYTOSOL TO THE CYTOPLASM OF THE HOST CELL. EFFECTOR PROTEINS INTERACT WITH SPECIFIC HOST CELL TARGET PROTEINS AND MANIPULATE THEIR FUNCTION TO FAVOR THE ESTABLISHMENT AND SPREAD OF INFECTION. AS SUCH, IT IS ESSENTIAL TO UNDERSTAND THE ROLE OF THE INDIVIDUAL EFFECTORS, INCLUDING EACH SPECIFIC HOST TARGET PROTEIN, THE MODIFICATIONS MADE TO IT BY THE E. ICTALURI EFFECTOR, AND THE CHANGES THAT OCCUR IN THE HOST CELL AS A RESULT. KNOWLEDGE OF THE TARGET PROTEIN FOR EACH EFFECTOR WILL LEAD TO THE DEVELOPMENT OF TESTABLE HYPOTHESES CONCERNING THE FUNCTION OF ANY GIVEN EFFECTOR OR COMBINATIONS OF EFFECTORS. THE ULTIMATE GOAL IS TO COMPLETELY CHARACTERIZE THE ROLE OF ALL NINE OF THE KNOWN E. ICTALURI EFFECTORS IN PATHOGENESIS IN ORDER TO DEVELOP INTELLIGENT VACCINE STRAINS BASED ON THAT KNOWLEDGE.