Abstract 5917: Development of a medium-to-high throughput organoid-bacteria co-culture platform for the assessment of host pathogen interaction

Abstract

Abstract Pathogens such as colibactin-producing bacteria strains of the Enterobacteriaceae family are highly prevalent in the gut microbiota of colorectal cancer (CRC) patients. 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. Studies conducted by Pleguezuelos-Manzanos et al. (2020) showed that repetitive cycles of colibactin-producing bacteria into the organoid lumen via microinjection, led to two co-occurring mutational signatures appearance, a single-base substitution signature (SBS-pks) and an indel signature (ID-pks), identified in a subset of CRC patients (~2% and 7%, respectively). These results highlight the relevance of organoids for modelling host-pathogen interactions and the application of these systems as in vitro platforms for investigating long-standing cause-correlation relationship between the presence of genotoxic pathogens and CRC development. The limited scalability of sophisticated co-culture strategies with pathogens such as microinjection has represented a bottleneck in the use of organoids as throughput screening tools in the development of preventive therapies. Thus, there is an unmet need to develop alternative co-culture systems compatible with the process of compound screening. An organoid-bacteria co-culture system compatible with medium-to-high throughput screening readouts has been developed. This co-culture system is currently tailored for the modeling of colibactin genotoxic effects in the gut epithelium, but theoretically could be extended as a discovery platform to identify targetable, novel and complex interactions between host and pathogen. Key words: colibactin, organoids, CRC, screening Citation Format: Eider Valle-Encinas, Roshni Nair, Katerina Pisa, Mayke Doorn, Farzin Pourfarzad, Lani San Mateo, Nicole Desch, Prashanth Gokare, David Pocalyko, Sylvia F. Boj, Carla Verissimo. Development of a medium-to-high throughput organoid-bacteria co-culture platform for the assessment of host pathogen interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5917.