Bacteria have developed mechanisms to communicate and compete with each other for limited environmental resources. We found that certain Escherichia coli, including uropathogenic strains, contained a bacterial growth-inhibition system that uses direct cell-to-cell contact. Inhibition was conditional, dependent upon the growth state of the inhibitory cell and the pili expression state of the target cell. Both a large cell-surface protein designated Contact-dependent inhibitor A (CdiA) and two-partner secretion family member CdiB were required for growth inhibition. The CdiAB system may function to regulate the growth of specific cells within a differentiated bacterial population.

Summary Contact-dependent growth inhibition (CDI) is a phenomenon by which bacterial cell growth is regulated

2517 Romiplostim is a peptibody that increases platelet production via binding to the thrombopoietin (TPO) receptor. This molecule has been engineered to have no amino acid sequence homology to endogenous TPO (eTPO); however, a low theoretical risk of developing conformational antibodies that cross-react with eTPO does exist. The current immunogenicity assessment strategy detects antibodies that bind to romiplostim, TPO, or TMP (the active peptide portion of romiplostim) and identifies any antibodies capable of neutralizing the biological effect of the drug or TPO. In clinical studies, 537 subjects with ITP were dosed with romiplostim; 31 (5.8%) subjects developed binding antibodies to romiplostim and 21 (3.9%) subjects developed binding antibodies to TPO. However, only 2 (0.4%) of these subjects had antibodies that neutralized the biological effect of romiplostim. The binding antibodies detected against romiplostim were not cross-reactive with TPO in the immunoassay and did not neutralize TPO in the biological assay. Pre-existing binding antibodies against romiplostim were detected in 43 (8.0%) subjects and against TPO in 29 (5.4%) subjects. The immunogenicity rates in Japanese ITP subjects (n=46) dosed with romiplostim were comparable to non-Japanese subjects. As a part of the post-marketing risk management strategy, Amgen performed immunogenicity testing on 37 subjects. Of these subjects, 3 developed binding antibodies against romiplostim that were not cross-reactive with TPO. None of these subjects developed neutralizing antibodies to romiplostim or TPO. The impact of immunogenicity to romiplostim on safety and efficacy was evaluated utilizing platelet profile as a pharmacodynamic marker. No significant impact of the antibodies against romiplostim and TPO on the development of adverse events was noted. Grade 3 and above hypersensitivity related events were found in subjects that were antibody-positive and antibody-negative in the same proportion, indicating that these events were not related to anti-romiplostim or anti-TPO antibodies. No clinical correlation could be made between the development of antibodies against romiplostim and/or against TPO and the previous drug therapies or concomitant medications. No correlation between binding antibodies to romiplostim or TPO and platelet profiles of these subjects could be established. The subjects that developed a neutralizing antibody response against romiplostim were associated with a trend of lower platelet counts. The reduced platelet counts could be attributed to the presence of binding and neutralizing antibodies to romiplostim. Alternatively, the lowering of the platelet counts could also be attributed to discontinuation of therapy at the end of study. Disclosures: No relevant conflicts of interest to declare.