Abstract 242: Development of organoids-bacteria co-cultures for medium-to-high throughput screening

Abstract

Abstract HUB patient derived organoids, (HUB-OrganoidsTM or PDOs) are self-organized epithelial cell structures with near-physiological features, extensively used to model aspects of cancer initiation and progression. Microinjection of colibactin-producing pks+ E. coli into the lumen of PDOs resulted in the appearance of two co-occurring mutational signatures identified in a subset of colorectal cancer (CRC) patients, demonstrating that pks+ E. coli plays a causative role in CRC development. The scalability of PDO bacteria microinjection is, however, limited and represent a bottleneck in the screening of preventive therapies for these patients. Here we develop a bacteria-PDO co-culture system (PDO-fragment exposure model), alternative to PDO microinjection, that is compatible with medium-to-high throughput screening methods. We validated the genotoxicity of colibactin-producing bacteria and showed the potential of the PDO fragment exposure model for the screening of drugs targeting colibactin-dependent genotoxicity. Citation Format: Eider Valle-Encinas, Mayke Doorn, Farzin Pourfarzad, Lani San Mateo, Prashanth Gokare, David Pocalyko, Sylvia F. Boj, Carla S. Verissimo. Development of organoids-bacteria co-cultures for medium-to-high throughput screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 242.