Abstract 1159 Changing the Target of a Bacterial Contact-Dependent Inhibition System

Some Gram-negative bacteria kill other bacteria in their local environments using contact-dependent inhibition (CDI) systems. These contact-dependent systems deliver protein toxins into the cells they target and are highly selective in which bacterial species and strains they kill. This selectivity derives from a specific interaction between a CdiA protein on the surface of the E. coli producer cell and a receptor protein on the surface of the E. coli target cell. Through crosslinking studies and mutational analysis, we have characterized how an E. coli CdiA specifically recognizes its receptor BamA on the surface of other E. coli cells. We have further identified specific amino acid substitutions that reduce this CdiA's affinity for E. coli BamA and increase its affinity for K. pneumoniae BamA. These studies provide an initial proof-of-concept that CdiA variants could potentially be rationally designed to selectively kill a Gram-negative organism of interest, such as K. pneumoniae. Acknowledgements to the College of the Holy Cross and the Cottrell Scholar Award #28179 sponsored by Research Corporation for Science Advancement.