The ever-increasing prevalence of bacteria harboring extrachromosomal elements or plasmids that confer resistance to chemotherapeutic drugs, that specify production of surface antigens, hemolysins, bacteriocins, toxins and other invasins and/or that alter biochemical traits so as to make clinical identification difficult, is causing curtailment of bacterial infectious diseases to be increasingly more difficult and therefore constitutes a threat to the public health. The objective of our research is to study transmission and functions of plasmids in gram-negative bacteria so as to be able to develop means for effective control and treatment of bacterial diseases. Most of the research will be concerned with Escherichia coli, Shigella flexneri and their plasmids. During the coming year, we will specifically investigate: a) use of translocatable drug-resistance determinants for the isolation and characterization of shigella flexneri mutants that are defective in invasion and/or intracellular multiplication; b) mechanisms for P1-mediated transductional transmission of plasmid replicons as influenced by plasmid size and copy number; and c) the influence of restriction as a barrier to the conjugational transmission of conjugative R plasmids among natural isolates of E. coli. We will utilize the technologies in microbial genetics, molecular biology, immunology and electron microscopy in this research.