Team UOregon


Helicobacter pylori (H. pylori) is a gram-negative bacterial pathogen that, as of 2015, resided in the gastrointestinal tract of an estimated 50% of the world’s population1, largely affecting developing countries and communities. H. pylori colonizes the gastric mucosa in the stomach, and infections are linked to mucosal lymphoma, gastritis, the formation of peptic ulcers, and gastric cancer2, even in asymptomatic individuals. Furthermore, certain lifestyles or exposures can trigger increased virulence and aggression towards the host. H. pylori has a unique set of evolutionary adaptations that allow it to colonize the stomach very effectively, making treatment difficult. The current standard of care is multiple rounds of a multi-drug cocktail including potent broad-spectrum antibiotics, proton pump inhibitors. These treatments are extremely harsh on patients’ bodies and intestinal microbiomes, and only somewhat effective, varying widely depending on drug choice with a pooled eradication rate of 79%3.


Our solution to the inefficacy of current treatments is an engineered, probiotic strain of E. coli (Nissle 1917) that possesses bactericidal characteristics specific to H. pylori. Nissle 1917 is already used as a probiotic(for competitive colonization and microbiome balance), and in the US is sold under the brand name Mutaflor ®, and has been granted Generally Recognized as Safe (GRAS) status by the FDA. Our engineered strain will differ by specifically recognizing H. pylori cells and delivering a malicious DNA payload through horizontal gene transfer. This malicious plasmid will inhibit H. pylori biofilm formation, forcing it into the more vulnerable motile growth form, and promote intraspecific horizontal gene transfer to spread our payload throughout the H. pylori population, killing the pathogenic cells.

We are taking a uniquely modular approach that will allow future work to modify our platform to be targeted towards nearly any pathogenic GI tract bacteria, and allows us to develop these parts in parallel. Other common pathogen examples, such as Salmonella typhi(responsible for typhoid fever) and Enterotoxigenic E. coli, could also be targeted using our potential system.

  1. We are computationally designing De Novo binders for unique surface features of H. pylori. These binders will determine the specificity of our conjugation machinery, and allow us to deliver our genetic payload exclusively into target cells. Our computational protocols can be trivially adapted to target surface features of any well characterized pathogen. We have created a piece of software, EZBinder, which can generate binders for any protein with high in silico success rates.
  2. We are engineering acid resistance into our cells using GadE to activate the glutamate dependent acid resistance mechanism of E. coli, as well as expressing a biofilm using an refactored curli pathway under the control of an arabinose-inducible promoter
  3. The strain of Nissle that we are using contains three landing pads in its genome. We will integrate our curli operon into one landing pad, gadE in another landing pad and leave the third site blank for a chemotaxis pathway. Future work should focus on populating this site and developing a chemotaxis system that works across a urea gradient.

By engineering a variety of biological systems for stomach colonization, navigation to H. pylori, and conjugation to deliver a fatal DNA payload, we are able to create an E. coli-based therapeutic that is specific, modular, and safe. Our E. coli-based solution does not rely on the use of antibiotics, which can be harmful when used repeatedly in high doses, and are becoming increasingly ineffective against bacterial infections3.

Future directions:
  1. Future iGEM teams can build on our work with curli and add other functionalities to the csgA monomers. We investigated using an H. pylori urease inhibitor, H. pylori surface binders, and even a ferritin domain for magnetotaxis. These functionalities could also be replaced with ones more relevant to other pathogenic bacteria (binders to bacterial adhesins, flagellar tip proteins, etc.) in different locations of the GI tract.
  2. We had planned to create a urea-inducible chemotaxis system, but it wasn’t effective enough to navigate urea gradients at physiological concentrations.


  1. Hooi, James K.Y., et al. “Global Prevalence of Helicobacter Pylori Infection: Systematic Review and Meta-Analysis.” Gastroenterology vol. 153, no. 2, Aug. 2017, https://doi.org/https://doi.org/10.1053/j.gastro.2017.04.022>
  2. Blaser, Martin J. “Who Are We?” EMBO Reports, vol. 7, no. 10, 2006, pp. 956–960, https://doi.org/10.1038/sj.embor.7400812.
  3. Fekadu, S., Engiso, H., Seyfe, S. et al. Effectiveness of eradication therapy for Helicobacter pylori infection in Africa: a systematic review and meta-analysis. BMC Gastroenterol 23, 55 (2023)https://doi.org/10.1186/s12876-023-02707-5