Due to competition for resources in microbial communities, bacteria have evolved mechanisms to communicate and compete with each other. One such mechanism is Contact-Dependent Growth Inhibition (CDI). CDI is a Type V secretion system found throughout the Gammaproteobacteria. CDI-expressing cells cause growth inhibition by delivering toxic proteins directly into neighboring bacteria upon cell-cell contact. In order to deliver toxins, CDI-expressing bacteria must engage specific receptors on the surface of neighboring cells. Although laboratory strains of Escherichia coli lack O-antigen, the pathogenic strains in which CDI is often found are coated in O-antigen in their natural environment. Previously, CDI has only been studied in the context of E. coli  K-12, a laboratory strain lacking O-antigen. This study aims to explore the effects of O-antigen on the growth inhibition efficiency of CDI-expressing bacteria. We have found that target strains expressing O-antigen are resistant to CDI in liquid co-culture, but are just as sensitive to inhibition when grown on a solid surface. Our results suggest that measuring inhibition in liquid culture is likely not a biologically relevant assay, and should instead be conducted on LB-agar. Future studies should be conducted on Proteobacteria with known differences in LPS composition, such as Burkholderia thailandensis, to test for its effects on inhibition. The results of this study will aid in our understanding of how we can more closely mimic the host environment in the laboratory, and future studies may help elucidate the mechanism of target cell engagement during toxin delivery.