Authors

E Valle-Encinas¹; R Nair¹; M Doorn¹; K Pisa¹; F Pourfarzad¹; L San Mateo²; N Desh²; P Gokare²; D Pocalyko²; SF Boj¹; CS Verissimo¹; 
¹ HUB Organoids, Netherlands;  ² Janssen R&D, United States

Discussion

Introduction
HUB!s patient derived organoids, (HUB Organoids® or PDOs) are self-organizing 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 results 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. However, the scalability of bacteria microinjection in PDOs is limited and represents a bottleneck in the screening of preventive therapies for patients. Here we developed a bacteria and 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.